From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
Chromosome
I. Aneuploidy
By
of
D.
JANET
Studies
Group
RowLEY,
\Vith
C Chromosomes
T IS NO\\’
ESTABLIShED
abnormalities
of
( leukemic
) cells
considerably
chromosomal
cells,3
precise
remains
to
he
systematic
normal
minating
in the
a relatively
ently
arising
manifest.
of chromosome
progressing
not
disorder,
iiovo,
amid
However,
importance
of
preleukemic
sified
the
the
more
and
the
further
third
requiring
no
disorders
exhihiting
morphologic
disturhed
formation
of any,
(erythroid,
ages
tic,
the
or
From
the
Research
work
the
of
of
First
Chicago,
time Lederle
submitted
D.
JANET
Jul,1
University
Hospital.
RICHARD
of
LEON
0.
pitals
and
Cancer
of
Clinics,
St.
part
Medical
Faculty
1965;
accepted
a
Cimicago,
for
Al-
group
the
major
blood
cell
of
and
the
United
of
line-
the
following
time
of
l)lOOd
aplas-
features
The
Chicago
clas-
often
examples
Argonne
Cancer
States
Atomic
the
Clarence
I.
lime.,
Irwin
Memorial
South
Bend,
Research
lnd.
Dr.
Fund
Blaisdell
and
is
the
Award.
for
Division
publication
Oct.
Associate
and
M.D.:
and
Professor,
of
time
Hospitals
BLAISDELL,
M.D.:
of
County,
Researcim
Hospital.s’
Dean
by
Joseph
Cimicago
K.
of
University
to
and
displaying
conditions.
be
designations
characteristic
yet
These
may
refer
not
the
disorders.
marrow
the
a
assess
leukemia.
conventional
the
stites,
with
to
of
is
clinically
syndromes
syndromes
of
Universiti,
the
cul-
appar-
opportunity
are
in
these
pre-
lii.
in
M.D.:
Chicago
JACOBSON,
Research
2,
ROWLEY,
Medicine,
University
hi1
of
terms
leukemic
the
and
leukemia
until
mveloproliferative
combination,
Medicine,
supported
Society
the
an
myelodysplasias4’5
between
(operated
was
Cancer
recipient
any
recognized
leukemic
megakaryocytic),
or
Department
Commission),
ThLc
or
transitional
Hospital
Energy
the
with
acute
pathogenesis
evidence
granulocytic,
myeloproliferative,
intermediate
by
elaboration,
accrue
sporadically,
hematologic
the
these
state
would
phase
human
affords
and
of
of leukemic
issue
occur
not
certain
potentially
vary
these
individuals.
is usually
myeIodsplastic,
may
leukemic
preleukemic
of which
in
affected
that
l)eginning
the
leukemia4
precisely,
this
Oh
l)ecause
alterations
aplastic,
first
bearing
of
acute
but
of the
exhibit
the
it is presumed
behavior
cases
occurrence
in
chromosomal
or,
into
though
the
terminate
in
evolution
forthcoming
disease
leukemia
ieoplastic
in affected
most
the
acute
constitution
stage
been
rare
with
the
through
leukemic
Iikuta,
to the
in
Patients
JACOBSON
on morphology
in any
one patient,
evidence
subject,
has
to
related
0.
LEON
Although
changes
Direct
overtly
de
propensity
are
of such
Three
Sliepley
patietits
constant
analyses
evidence
still
mans’
to another.”2
determined.
sumably
Such
be
patient
role
Lona
number
may
one
abnormalities
the
from
that
AN!)
of Judith
and
chromosome
which
from
Byrne
in
BLAISDELL
assistance
tCC/lfliC(1l
Rachel
I
K.
RICIIAIID
time
in Preleukemia
Clinics,
and
Department
of
time
Professor,
the
of
the
Professor),
and
Assistant
Clinics,
1.955.
21,
(Assistant
Cancer
Department
Argonne
Medicine,
Biological
Department
Argonne
of
Cancer
Research
Universiti,
of
Sciences,
and
of
Research
Medicine,
Hospital.
Chicago
Director,
HosArgonne
Hospital.
782
BLOOD,
VOL.
27,
No.
6
(JUNE),
1966
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
STUDIES
illustrate
the
aplastic,
anemia,
heterogeneity
primary
implicated,
of
covery
may
anemia,
group
and
most
cases
its
Although
most
in
yet
separateness
from
the
leukemic
classes
: refractory
hyperplastic
atypical
myeloid
disorder,
preleukemic
acute
hematopenia.
etiology
ensue,
this
and
splenic
the
783
PRELEUKEMIA
myeloproliferative
sideroachrestic
leukemia,
he
IN
cases
are
fatal
certain
remains
causal
factors
oI)scure,
and
after
conversion
or terminate
might
although
re-
to
acute
leukemia.
Only
five cases
of persistent
abnormalities
been
reported
in patients
with
potentially
of chromosome
morphology
leukemic
disorders,
in whom
kemic
in
transformation
has
leukemia
karyotypes,
During
the
obscure
was
three
yet
the
C group
leukopenia,
developed
with
acute
and
classes
first
have
although
these
existence
of
no
karyotypic
chromosomal
important
aneuploidy
at this
is to consider
and
with
potential
to
other
leukemia
to
with
a stable
Chromosome
technic
preparations
of
Tjio
centrifuge
cial
and
tube
(1000
centrifuged
warm
After
at
(37
600
C.)
r.p.m.
for
20
was
discarded.
the
5
of
ml.
fixative
45
changed
This
The
fixative.
were
Giemsa
Peripheral
37
C..
centrifuged
glacial
daily
bloOdi
was
mounted
was
the
at
standard
in Histoclad
cultured
of
0.5
cases
altera-
cases
was
of
patients
10
added
minutes
at
600
in
5 ml.
of
the
cell
cells
per
cent
during
requfred
this
technic;’4
period.
they
were
stained
37 C. and
at
8-10
The
material
r.p.m..
fresh
ml.
of
was
and
the
1:3,
glacial
was
centri-
resuspended
This
suitable
than
in
second
quality
a dozen
preparations
with
were
changes
of
of
Leishman-
Inc.).
the
technic
of Moorhead.’5
a
commer-
and
methanol.
Slide
were
of
suspension
of
more
in
put
vincaleukoblastine
1 hour
added.
the
marrow
was
ml.
discarded.
preparations
and
0.1
of
was
and
1)One
1 ml.
for
was
55
direct
solution
minutes,
and
the
incubated
for
(Clay-Adams,
imsing essentially
of
solution
chromosome
air-dr
hypoth-
these
approximately
resuspended
45
C.
any
leu-
cell-line.
sg./ml.
was
removed,
-4
similar
which
citrate
week
in
the
overt
chromosomal
abnormal
supernatant
acid
until
over one
stored
an
After
was
that
of
in presenting
report
to
gently
acetic
took
by
made
and
were
fixative.
twice
material
then
stain
sodium
cells
the
likely
onset
considered
modification
sample
cent)
supernatant
occasionally
of
the
per
at
cent
per
ml.
minutes;
The
fixative
0.1
10
methanol,
first
was
obtained.
cells
minutes
acid:absolute
fuged,
it seems
the
of the
sample
solution
mixing.
(0.95
a
marrow
hank’s
and
for
hypotonic
supernate
acetic
of
thorough
incubated
and
l)een
chromosomes
This
METHODS
using
bone
5 ml.
units/mI.)
Lilly).
made
The
containing
heparin
(Velban,
were
Whang.la
AND
three
has
47
significance
MATERIALS
of the
anemia
before
investigators
associated
sideroachrestic
sideroachrestic
observation
which
should
be
and leukemia.
Our purpose
encourage
The
to above.
in leukemia,
possible
to
instance.
included.’2
was
abnormalities
the
whom
is confined
example
an
have
of
referred
with
all terminate
we
idiopathic
in
anemia
manifested
none
in each
syndromes
analysis
may
kemia
is an
esis relating
time
aplastic
who
abnormality
being
abnormalities
of
conditions
such
the
anemia,
hematologic
examined.6’5”
numbers,
alteration
aplastic
of chromosome
A case
Since
tion
I)een
abnormal
thrombocytosis,
chromosome
case,
first
with
patients
or
In each
cases
was
leukemic
thrombocythemia-each
thrombocythemia.
other
marrow
it is a different
leukemic
report
reported,
leukemia.
idiopathic
of potentially
is the
abnormal
but
diagnoses
anemia,
the
all
thrombocytopenia
chromosomes,
respective
when
of 15 potentially
individuals
has
occurred;#{176}
evident
investigation
anemia,
found
not
have
leu-
The
leukoc’ytes
the
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
784
were
separated
minutes.
from
The
tinin
NI ( Difco).
culture.
which
Buccal
the
buffs’
red
coat
Velban
was
smears
by
centrifuging
removed
and
added
either
was
usually
were
cells
was
after
about
preparer!
the
added
heparinized
blood
TC
medium
or
for
AND
at
199,
600
with
2 hours
JACOBSON
r.p.m.
for
10
phytohemagglu-
before
terminating
the
hours.
according
to a modified
technic
of Ross.’1’
REPORTS
1
A 23-year-old
1963,
white.
when
larly
was
he first
unmarried.
noted
prescril)ed.
subsided,
totaling
April
days.
given
throat.
As
a
years.
for
painter.
No
solvents
r
There
the
to the
was
mental
1964.
a sore
patient
hemmatologic
spray-painter
of the
he
1964.
had
Cm.
to
used
and
been
well
until
oral1’
a 3-week
frequent
course
lacquer
had
during
have
a second
apparently
Chloramphenicol
16.0
began
examinations
was
buttocks.
approximately
progressive
was
male
furuncles
but in January
weakness.
In
The
easy
various
thinners
prior
3.0
for
infection
bruising,
of chloramphenicol.
1)erformed
intramuscu-
period.
epistaxis.
November
and
the
and
Cm.
over
previous
to exposure
4
three
to the
volatile
chloramphenicol.
no
family
history
of
a similar
illness.
other
hematologic
disorders.
or
develop-
anomalies.
When
seen
revealed
the
BLAISDELL
overnight
72
CASE
Case
to
ROWLEY,
lymph
hair
at
the
pallor
University
and
of Chicago
petechiae
nodes,
the
over
spleen
or
Hospitals
the
the
on
extremities.
liver.
He
Mas
15.
There
had
1964.
was
no
adult
normal
plwsical
examination
palpable
male
enlargement
external
of
genitalia
and
distribution.
Laboratory
exam,iination
ml..
reticulocvtes
per
cent.
The
0.1
cent,
lymphocytes
77
granulocvte
were
disclosed
per
Xg
activity
per
alkaline
(a+).
within
of
cent,
and
score
limits;
starch
81
hemoglobin
with
mm..
4 per
was
for
cent,
per
3000/cu.
monocvtes
hemolysates
normal
21
leukocytes
phosphatase
Assays
were
hematocrit
total
cent;
(normal
and
15
to
Cm./100
neutrophils
platelets
range
ghicose-6-phosphate
gel
6.8
segmented
50).
The
revealed
the
mm.
red
dehydrogenase
electrophoresis
19
4400/cu.
cells
(C-6-PD)
normal
G-6-PD
B
pattern.
Sternal
tion
hone
of
marrow
sections
granulocvtes.
elements
liv
showed
erythroid
tissue.
fatty
pronounced
precursors.
No
abnormal
hypocellularitv.
and
cells
with
niegakarvocytes.
were
seen.
and
Excessive
substantial
reduc-
replacement
stainable
of
iron
these
demon-
was
strated.
The
pancvtopenia
therapy
blood
September
pmtients
marrow
as
April
1964.
and
after
hemoglobin
examination.
a persistent
When
most
a lift
l)ut
to respond
failed
1964.
only
to iron,
transient
liver
benefit
extract.
had
folic
been
acid,
noted
and
after
vitamin
four
B
12
separate
transfusions.
In
ity.
had
during
paucity
recentl’
machine
recent
normal
moderate
leukopenia
percentages;
the
of oral
of myeloid
seen
on
operator.
l)tmrPuric
renmained
4 months
value
rose
to
7 months
after
lesions
in
cells
Max’
was
were
evident
of
has
persisted
fluoxvmesterone
Cm./
100
preceding
and
14.
There
spite
severe
15.9
the
still
the
no
on
in
(white
his
count
(platelets
thrombocvtopenia
no
had
The
3200/cu.
hemoglobin
10
mm.)
7700/cu.
returned
to
of hemopoietic
to
mug.
with
mm.)
has
the
hone
activ-
of leukemia.
and
patient’s
dosage
daily,
mg
another
erythroid
evidence
married
enlargement
limbs.
androgen
cell
but
patient
palpable
40
In
February
1965.
revealed
moderate
megakaryocvtes.
1965.
a reduction
(Halotestin)
ml.
one,
level
daily.
has
However,
normal
not
work
organs,
a
differential
improved
sig-
nificantly.
The
diagnosis
probably
related
1w androgen
Case
This
November
has
to
been
aplastic
chioramphenicol
anemia
and/or
(marrow
organic
panhypoplasia
solvents,
with
with
partial
pancvtopenia)
remission.
induced
therapy.
2
62-year-old
1961
mian
his
spleen
was
found
was
to
removed;
have
a
severe
it weighed
refractor
746
Cm.
anemia
and
in
exhibited
July
1961.
“hperenmia”
In
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
STUDIES
microscopically.
This
(approximately
failed
of iron)
hepatomegal.
Family
history
Although
and
patient
thus.
Examination
the
of
palpable
the
time
revealed
heart.
lymph
and
Blood
examinations
1.80
The
admission
32
1011/cu.
per
cent,
to
edema.
17
units
of
1)lood
1963.
mental
noted.
each
the
The
genitalia
had
wife
University
mean
was
were
of normal
6.5
cell
reticulocyte
of
dermal
liver
hemoglobin
ismi..
and
of
In January
illnesses.
brown-grey
external
disclosed
x
were
twice.
A total
period.
a hvsterectovmv
hadi
pn’
to
children.
confusion,
pedal
nodes.
cell count
concentration
of
mental
anemia.
a 4-year
or related
n,arrie(i
no
the
over
mellitus
similar
been
were
relieve
given
diiahetes
known
had
there
at
1. 1964.
no
to
were
and
included
the
marriage.
ment
Cm.
785
PRELEUKEMIA
preceduire
4.25
deterioration,
her
IN
slightly
Cni./
volume
count
Chicago
4.6
100
nil.,
en.
1)ut
size
and
there
20
total
were
per
cell
mmean
The
Novemimenlargeno
form.
hematocrit
cent.
on
moderate
enlarged.
male
1 10
per
I hospitals
pigmentation.
cent,
red
hemoglobin
leukocvte
count
was
( corrected
for norn,oblastemia
) . with
segmented
neutro1)hils
44
cent.
lymphocytes
44 per cent, monocytes
10 per cent, eosinophils
1 P’ cent,
and
basophils
1 per
cent. The platelets
numbered
252.000
to 607.200
per cu. mm.
Red
cell aniso-p()ikilocvtosis.
hypochromuia.
iron-positive
inclusions.
target
cells and 94 nucleated
ervthrocvtes
P’
100
white cells were seen in the blood smears.
8200/cu.
mm.
Sternal
marrow
plasia.
with
with
stainable
material
aspirated
a predominance
iron
of
inclusions
in
earl
( “ring
1964
and
) . There
sideroblasts”
intense
an
was
no
of
evidence
and electron
microscopy
revealed
heavy
aggregates
of iron
in the
normoblasts.
which
is consideredi
to be
characteristic
of certain
A second
marrow
examination
on April 20. 1965. just prior to (leath.
significant
Death
followed
heart
diagnosis
the
absent
Case
cells
was
mitochondria
sideroblastic
revealed!
no
with
pneumonia
with
septicemia.
progression
to
The
hemoc’hroma-
revealed
with
no
of the
chronic
liver
a diagnosis
of
evidence
of
basement
disease;
the
leukemia.
membrane
but
Klinefelter
Histologic
of
the
examination
tubules.
showed
mio
svndrone.
3
This
59-year-old
Negro
melena.
No
requiring
blood transfusion.
similar
illness
or hematologic
The
1945.
Since
housewife
in
patient
had
rhage
had
within
January
a somewhat
vascular
occlusive
Laboratory
when
four
episodes
1960
x-ray
examination
known
in the
and in
disorder
and
There
with
of the
patient
no
corpus.
no external
abdominal
at
seen
normal
Neither
age
with
with
a duodenal
ulcer.
at
the
49.
However,
profuse
although
uterine
henmor-
pregnancy.
the
adult
evidences
extrac-
distress
family.
of each
first
dental
revealed
abortions
beginning
was
following
upper
menopause
deformities,
uterine
were
was
bleeding
of
spontaneous
months
the
prolonged
history
disclosedl
cervix
enlarged.
noted
had
4 occasions.
a few
1964.
small
palpably
first
had
menstrual
on
examination,
on
she
pregnant
occurred
Physical
were
1956.
a normal
had
become
Hospitals
hut
and
hvalinization
to support
tions
she
of
iron
the heart.
and
consistent
of Leydig
and
anemia.
diagnoses
showed!
spermatogenesis
prominence
skin
clinical
testes
fibrillation.
sideroachrestic
pancreas.
the
of the
atrial
idiopathic
liver,
confirmed
examination
failure.
was
involving
Autopsy
and
Stainable
change.
clinical
tosis
formation.
hyper-
nornoblasts
morphologic
pronounced
anemias.17
megakaryocyte-platelet
erythroid
abundance
granulopoiesis
marrow
altered!
showed
precursors
disturbed
of
or
November
ervthroid
University
female
liver,
of
external
Chicago
genitalia.
nor 1vmmph nodes
and no signs
of
spleen.
of hemorrhage
disease.
showed
a hemoglobin
value
of 10.4 Cm,,./100
ml..
hematocrit
34
per cent. mean cell volume
77 cu. microns.
mean cell hemoglobin
concentration
31 per cent.
reticulocytes
1.9 per cent,
plasma
iron 85 tg./100
ml.
and
unsaturated
transferrin
300
sg./100
ml.
In the blood smear,
the red cells were hvpochromic.
Total leukocytes
numbered
10,100/cu.
mm..
with neutrophils
76 per cent.
lymphocytes
15 per cent,
monocytes
3 pe
cent,
mm.
and
eosinophils
Cranulocyte
Sternal
platelets
examinations
marrow
were
6 per
alkaline
sections
unusually
cent.
phosphatase
revealed
prominent.
Platelet
counts
scores
normal
Stainable
varied
ranged
overall
iron
from
from
39
cellularity;
was
reduced.
667.000
to
to
1.375.000
per
cti.
104.
however,
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ROWLEY,
786
BLAISDELL
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CIJ.ROMOSOME
STUDiES
Following
on
one
iron
a peak
the
red
) was recorded.
the three marrow
After
mug.
daily;
but
787
PRELEUKEMIA
administration,
occasion
mg./Kg.
2-8
IN
cell
patient’s
volume
examinations,
only
after
one
hematocrit
busulfan
month
did
of
( Myleran
the
The
diagnosis
an(i
red
has
cell
diagnosis
been
volume
idiopathic
value
on
of polycythemia
platelet
iron
therapy
thrombocythemia;
one
vera
of the
1). In the
apparently
occasion
masked
Thirteen
55
per
cent
( normal
prescribed
counts
in
fall
however,
after
by
chronic
bleeding
to
and
23
oral
to
36
doses
the
of
20(),000
to
the
elevated
permits
and
iron
hemmiatocrit
consideration
the
of
deficiency.
STUDIES
of
addition
In
marrow
consistently
which
contained
these
cells
to one
or more
contrast,
the
Similar
sample.
Analyzed
from
with
morphology
to
have
or G-Y.
The proportion
first peripheral
This
may
Case
2
The
extra
phology.
and
were
a G,
chromosomes,
These
5 could
of breakage
was
too
two
extra
poor
increased
belonged
containing
In
second
This
to
missing
in both
higher
bone
than
fragility
of the
patients
in
metaphases
The
extra
none
E chromosome,
cell could
not
sample
3 months
be
5 had the normal
number
be normal
cells or, as seems
of a 47 chromosome
metaphase
specimen
2 cells
of the
2).
direct
F.
mar-
bone
the
first
In
an
sample
3 cells
extra
of
had
an
C and
were
poor
mor-
of
11 analyzed
of
cell
E,
medium-sized,
because
loss
the
groups
was
normal:
had
nor-
cells.
both
of chromosomes
quite
likely,
they
with
46
samples
and the
our laboratory.
mitotic
karyotyped
later
were
chromo-
but
for
first
chromo-
to
marrow
normal
clearly
46
the
had
certainty,
(Fig.
was
in
chromosomes
chromosome
C group
speci-
contained
of a C group
from
of one
marrow
belonging
cells
is much
in
loss
48 chromosomes;
with
chromosomes
to the
an
had
karyotype
small
46 chromosomes,
and
one
the second
45
blood
cell
and
46 chromo-
normal
loss
peripheral
exception.
had
bone
appeared
consistent
16
basis.
metaphases
containing
the
chromosome
number
was 47 (Table
1).
C and
missing
the
one
some
submetacentric,
6 cells
metaphases
showed
of hypodiploid
blood
specimen
reflect
modal
preparations
46
again,
cells
chromosomes
appeared
the
and,
C
the
chromosome,
random
second
group
of
karyotyped
group
blood
1/59
had
one
on a random
of the
chromosomes
and an
(Fig.
Nine
cells showed
breakage.
only
(Table
and
were
C
peripheral
analysis
However,
5/58
in detail
one
the
populations
metaphase.
apparently
from
on
later.
of
in detail
some
obtained
46 chromosomes
45 chromosomes
had
45 chromosomes
Hypodiploid
due to cell
presumably
had
each
lacking
of cells
cell
analyzed
from
than
two
cells
chromosomes,
karyotype.
Seventeen
some.
other
whereas
analyzed
were
consistently
7 months
chromosomes,
cells
less
cells
36/58
missing
was
were
5/58
whereas
majority
results
aspirated
revealed
specimen,
hypodiploid
was
somes
and a normal
or more chromosomes,
men,
chromosomes
karyotype,
of the
metaphases
each
marrow
first bone
normal
chromosome
the
of
1
Analysis
row
a high
mI/Kg.
) was
blood
CHROMOSOME
Case
mal
to
38.4
per cu. mm. range.
300,000
1).
rose
measurement
cells
with
in the C-X group.
could
be the result
a C group
chromo-
46
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
p
ROWLEY,
788
BLAISDELL
AND
JACOBSON
1
I
B
Z
:
6- 12
D
E
“
ts
13’-
16-
G
F.
w’3
.V
Fig.
1.-Case
45
Each
of
the
an
lacking
1
E,
and
chromosomes
one
other
2 were
chromosome,
assuming
in the
with
first
iii
sample,
6
analyzable
2
A
F
had
However,
had
an
from
in
extra
the
marrow.
cell
chromosomes
contaimmimig
lacking
an
had
of the
E.
some
2 extra
the
This
with
would
otie
C
extra
other
hvperdiploid
with
extra
2 were
an
a C p1tms
1)0th
preparation,
extra
an
a D,
of 5 metaphases
l)ut
breakage
second
had
lacking
One
48 chromosomes
C and
same
chromosome
C
were
resulted
bone
from
the
1 was
chromosomes.
and
4 mnetaphases
metaphases
46
chromosome,
C-Y
l)lmte
of
miissiimg.
cells with
an
an
the’
mmietaphase
karvotvpe
cllrOmllOsOmlle
lacking
other
the C group.
48 chromosomes
group
lacking
was
The
C
lacking
was
chromosome.
somes
Above:
Beh)mL’:
commtrast.
with
chromosome;
45
anemia.
using
chromosomes,
soiiw.
C
aplastic
1,
XY
21-.2z
1.9-20
photographed
18
line.
chromometaphase
suggest
that
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
STUDiES
IN
789
1’IIELEUKF;MIA
4,
li,1
,,p
F
*
A
B
frl’
2
3
6-la
D
E
13-15
F
16-18
G
.
zi-ac
19-ZO
Fig.
2.-Case
direct
bone
the
type
of
the
cells
2,
cell
with
48
out
contained
46
normal
were
showing
47
chromosomes
rather
than
Aboce:
photographed
c’hm’omuosomes
were
nietaphase
using
the
pIm
with
one
result
of
of an
representatives
plate
ol)tainecl
contrast.
extra
group
C
mitotic
stable
karvo-
chromosome.
accidents,
additional
from
Below:
such
as
hvperdiploid
line.
Forty
loss
anemia.
preparation,
above
nondisjunction,
stem
sideroachrestic
marrow
xv
of
49
cells
chromosomes.
a result
as
of
poor
obtained
chromosomes.
Cells
of breakage.
morphology,
from
Seventeen
with
The
hut
a
of
less
than
metaphases
the
extra
72-hour
these
were
46
periplier;tl
karyotyped
chromosomes
with
chromosomes
more
blood
and
showed
than
appeared
culture
revealed
random
46 chromosomes
to
be
small
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
790
BLAISDELL
ROWLEY,
and
could
with
belong
to group
a karyotype
obtained
from
the
11:4 thymidine
(tires
became
smears
were
to
the
)eripheral
have
Two
culture.
either
F, or C-Y,
similar
or could
blood.
contaminated
Two
amid
no
bone
the
marrow
metaphases
have
been
metaphases
marrow
were
cultures
with
were
obtained
established;
both
figures
( Barr )
No
in
JACOBSON
were
obtained.
from
ciiiBimecal
bodies.
3
Case
Two
distinct
( Table
and
cell
1 ). In the
had
an
lines
first
were
present
sample,
apparently
(Fig.
3).
normal
Metaphases
of this latter
chromosome;
some.
cell
the
The
same
two
karotype.
cells
would
be
No
expected
one
bone
cells
were
extra
present
cells had
analysis
resulted
of the
blood
appeared
and
and
ccii,
an
hypodiploid
chromosomes
C’s
had
in
the
in 27 per
cent
of
group
from
C
breakage
and was without
a D
one extra
C chromosecond
bone
marrow
metaphases
was lower.
This
used
to study
the H3 thymidine
Sandberg
and
colleagues
have
not
tolerate
in vitro
C group
culture
chromosome
was
found
in
the
peripheral
blood
as well
as
found,
as
culture.
from
random
loss of chromosomes
cells with
46 chromosomes
revealed
had inconsistent
to he two extra
E and
abnormalities
C chromosomes,
a C in the
this apparent
relationship
seems
doimhtful.
cells,
one appeared
to have
7 A group
mass
ran-
Nine
in
resulted
other
cell.
to be related
to the cells with
48 chromosomes
since no hyperdiploid
cells have
been
found
second
seemed
to have
C replacing
a D group
with
cells.
female.
were
cells in the peripheral
In 2 such cells there
specimens
46 chromosomes
of diploid
probably
do
marrow
contained
cells
two
late-labeling
in a normal
cells
an F in one
with
were
marrow
Only
hyperdiploid
appear
however,
two
to breakage
47 chromosomes
stem-lines
l)one
do.
hypodiploid
cells. Detailed
Six
due
the proportion
of hyperdiploid
to the 6-hour
culture
period
of these
chromosomes.
As
aneuploid
diploid
the
line, as one metaphase
had 2 extra
other
2 cells
with
47 chromosomes
I)reparation,
but
might
be related
labeling
pattern
shown,’5
with
in
27 of 46 metaphases
dom loss of one or more
chromosomes
46 metaphases
had 48 chromosomes
tin
found
6-hour
mitotic
for sex chromatin
fragments.
line
been
done;
no labeled
separate
skin
cultures
negative
be
hyperdiploid
AND
Of
an extra
C in place
chromosome.
Buccal
of 200
cells
the
diploid
5 of 17
in the karyotype.
replacing
a D
These
two
cells
found
in the
in the peripheral
other 3 abnormal
chromosomes
Most
from
that
while
yet
lacking
of an E, and the third
smears
showed
only
would
marrow;
blood,
diploid
a C;
had
1 sex
the
an extra
chroma-
counted.
Disc;ussmox
Our
et
3 patients
all
group.
3 of
These
tent
row;
chromosomal
and
all had
apparently
marrow
illustrate
disorders
if the
with
had
cases
hematologic
the blood,
presented
them
must
investigation
aberrations
essentially
unm’elated
chromosomal
the principle
include
in
normal
that
a study
is to be
sonic
or
any
bone
All
in metaphases
the
examination
marrow
3 patients
all ITietaphaSeS
syndromes,
involving
cytogenetic
of the
coml)lete.
karyotypes
liematologic
abnormalities
from
as well
showed
the
from
hone
the
C
of
as of
persismar-
periph-
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
STUDIES
IN
791
PRELEUKEMIA
I
cg
ciIIF
-Il
I
‘as
Fig.
..
1,-a.
3.-Case
from a direct
bone
karvotvpe
of the
chromosomes.
21-22
3,
idiopathic
marrow
same
ccli
thrombocythemia.
preparation,
containing
Above:
photographed
48
chromosomes
x
metaphase
using phase
with
x
plate
obtained
comitrast.
Below:
2
extra
C
group
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
792
BLAISDELL
ROWLEY,
era!
cytes
blood.
cultured
scribed
are
sis-that
Case
In
No.
has
Patient
C
cells
anemia
presemice
B
normal
cells.
for
we
rescnt
alternative
female
normal,
sex
No.
the
buccal
chromosome
cussed
amid
the
Ili
five
abnormality
ics,
with
Case
cases
These
cells
that
patients
had
genitalia,
woman
who
severe,
The
involved
with
in
I)al)ers
stable
is given,
karvotvpic
cdlv
witlioimt
46
had
The
marrow
a
who
woman
chromosomes)
47
chromosomes),
the
with
our
trisomy.
The
No. 2, amid quadruple
following
reasons:
the
external
genitalia
normal
male
majority
and
2 should
is being
in
have
are
normal
Autoradiography
X chromosomes
only
have
Cases
No.
2
no late-labeling
one.
(This
that
of
no
have
been
previously
imi the developing
miormal
statement
X
dis-
is
47 chromosomes,
with
observed
a hone
marrow
in
but
and
trisomy
cells
from
examination
anomalies
hematologic
of
children
mosa-
propor-
in the
C group.
The
blood
and/or
skin;
any
in
of
skeleton,
with
were
a variable
the
the
abnormality,
whose
reported,2u
All
zygote.
chromosomes,
was
normal
was
congenital
myeloproliferative
of
low.
autosomal
Case
respectively.
developmental
and
majority
patients
normalities
the
compatible
occurred
containing
abmiormality
no mention
and/or
for
3 should
apparently
some
chromosome
there
was
with
46 chromosomes,
3 above.)
of group
C trisomiiv
of metaphases
tion
No.
indeed,
expense
remain
48
of
for
of late-labeling
correct,
Case
No.
are
the
to androgen
in
with
examples
complements,
number
the
chloramphenicol
karyotype
syndrome
are
that
1 and
in Cases
the
are
have
smears
the
responded
anemia
unlikely
seem
Xg
to chloramphenicol.
thrombocythemia
1)100(1
to determine
the
321
If our diagnoses
chromosome
marrow
C
the
period;
at
counts
for
of
possibility
that
of the
hypodiploid
a 7-month
piiteiet
specific
normal
the
has
in the
cells
indicate
increased
anemia
2 (sideroachrestic
3,
peripheral
amid
female
No.
over
alid
embryogene-
autosome
X-linked,
has
not
is that
they
of Klinefeiter’s
for Case
in the
cell
exposure
(idiopathic
interpretation
diagnoses
of cells
used
and
3
a
after
to Case
No.
1)lood
an
1)lOOd
thus
excludes
The
karyotype
patient’s
probably
found
red
are
apparenti
the
white
are
have
regard
Case
have
Clinically
)
patielit’s
constant
remained
after
congenital.
chromosomes
amid
JACOBSON
of the
implioabnormalities
de-
developed
not
which
cells
pancytopenia
With
45
chromosome.
has
his
have
the
in
C-6-PD2’
X
diploid
pattern
chromosomal
and
with
hypodiploid
changes
developed
-x
an
marrow
of
although
toxicity
and
an X chromiiosome
bone
chromosome
for
is
diploid
therapy,
ple,
band
have
in the
and
The
chromosome
proportion
cells
the
acquired
( aplastic
a
does
lost
marrow
lost.
1
and
to
)resumably
are
I)eeIi
antigen’9
of the 1rdomiiimiamitly’
the peripheral
blood,
confined
is, they
group
the
Because
from
AND
these
cases.
nervous
the
system.
exception
in 2 of 3 pregnancies
of
had
one
multi-
abnormalities.
of the
reported
patiemits
with
chromiic
addition
cases
mnveiogenous
to the Ph1
since
in most
abnormality
leukemriia.”
disorders,
of amieuploidv
leukemia,
for
especially
leukemia
miiay
ciiromosomne.27
of these
occurrimi
in Nowell
4 pati’mits
also
Hungerford’s
showed
marrow
C chromosomes
leukemia,
show
A review
presentations
g in a 1)Otemitiallv
and
group
acute
although
a1)-
chromosomal
of
there
is one
leukemic
repcm’tm
the
following
case
patient
of
chromiiosomnal
with
a
alleg-
7 cases
aberra-
of
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
tions.
STUDIES
Two,
patient,
trisomy
group
chromosome
chromosome.
The
verted
to
modal
hut
The
chromosome
in the
no signs
a
blood
and
than
“other
aberration.”
to
marrow
The
be
C group.
a D chromosome,
The
leukemia,
had
47
yielding
diagnosed
one
as myeloid
leukemia,”
one
with
all
suggestive
chromosomes
vera
x-radiation
to the
6 analyzed
patient
of
meta-
missing
E
leukemia;
mTiiSsing
polycythemia
and
This
l)One
from
who
mTiarroW
only
omie in whom
the
received
had
a modal
cells
in an
the
either
had
spleen,
resulting
is the
studied
20
and foumid
karyotpic
with
showed
apparemit
a
extra
there
were
trisomy
C 9. Forty-seven
of
blood
on
a second
examination.
as
“chromosomal
occurred
leukemic-hike
peripheral
patients
p1tients
with
mycloproliferative
disoronly
one patient
with
a chromosomal
abnormality
“a possible
and
marrow
well
as
cells
abnormalities
on
the
of
were
seen
myeloid
x-radiation
marrow
by an
impression
metaplasia
to the
large
following
hones
that
the
long
arm
of one
abnormal
blood
count
of
cytes,
present
42,800
with
in
differential
the
This
cent
which
karyotypic
consist
occur
vera
well
abnormality
and
his co-workers,
which
evolved
from
patients’
radiation
Freireich
and
gaps,
in
reported
by
reported
three
and
patients
or niay
cases
that
with
a ter-
abnormalia patient
treated
and
deletion
an
5 per
no
of most
elevated
cent
white
metamyelo-
blasts
were
re-
of
leukemia.
It is also
to iomiizing
radiation.
is well knowmi.2”
These
fragments,
percentage
Nowell
the
had
Although
breaks,
in their
irradiated
these
aberramit
cells
therapy.
associates5
discussing
concluded
from
possibility
was
related
aberrations
a variable
bone
of one C group
chromochromosome.
It was
their
and
examination.
of achromatic
sporadically
in
hone
the
who
had been
as radiophosphorus,
patient
myebocytes
ported,
these
blood
cell findings
raise
the
conceivable
that
the chromosomal
change
That
irradiation
can produce
chromosomal
aberrations
as
consid-
in
in patients
resulted
autosome.
12 per
and
disorder.”
morphologic
chromosomal
Solani’s
group7
described
polcythemia
amid spleen,
of mye-
was
in both
Hungerford,
predominantly
chromosome
C group
found
collaborators,
amid
cells showed
a consistent
replacement
abnormally
short
acrocentric-type
of
of the
case
and
examinatiomi,
and
Noweil
unusual
phase”
were
initial
Samidberg
those
in an
terminal
chromosomes
minal
leukemic
stage
of the mveloproliferative
Goh and Swisher
found
mio consistent
ties in their 8 cases of myeboid
metaplasia.25
whose
some
of
a D chromosome
colleagimes
leukemia”
metaplasia
with
with
granulocytic
coumits
45, with
hut
of
to
case,
to subacute
chromosomes.
of leukemia.
Sandberg
their
46,
aJiTI
converted
by a chromosome
resembling
a C group
patient
with
polycythemia
which
had con-
a l)atiemit
of
long
had
C group
grantmlocytic
therapy
number
of the
chromosome
ered
fourth,
second
with
was
radiophosphorus
deletion
the
subacute
number
C or E group.
bid
In
to
myclofibrosis,
extensive
deletion
was
replaced
third
case was
chromosome
ders
C and
“converted
illness
involving
converted
a G chromosome.
which
whose
abnormalities
polycythemia
with
resembling
patients
had
with
chromosomes
plasia
three,
leukemia.
793
PRELEUKEMIA
or 1)oSsibly
granulocytic
first
IN
of
dicentrics,
and
cells.
consistent
Ilungerford,
The
and
may
represent
a
be emitirely
unrelated
of refractory
anemia,
by
rings,
Solani
stem-hue
to the
throm-
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
794
ROWLEY,
BLAISDELL
AND
JACOBSON
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From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
STUDIES
bocytopenia
had
only
IN
and marrow
chromosomes
45
cultured
peripheral
three
patients
died
Case
No.
but
Kiossoglou
and
Mitus,9
in chronic
granulocytic
and
one
blood
and
of “acute
semble
our
thrombocytopenia,
795
PRELEUKEMIA
hyperplasia,
missing
C
in which
the marrow
cells
group
chromosomne,
whereas
skin cells showed
myelomonocytic
1 with
regard
our patient
had
to cytogenetic
a very hypocellular
in a recent
myeloproliferative
46 chromosomes.
leukemia.”
These
abstract
syndromes,
an
extra
C
group
clinical
chromosome.
diagnosis
her bone
marrow
have
group,
whereas
peripheral
the
normal
diploid
formation.
If one
considers
2)
to
who,
only
for
a chromosome
C chromosomes
leukemia
repeated
relapses
mode
duration
resulted
each
showing
reveals
leukemia,
4 years
of cells
either
(or,
in
in
the C
contain
of leukemic
tramis-
reports
(Table
of the
5 show
4 out
deletion
of most of the
alternatively,
a double
Nowell
and
Hungerford’s
deletion
of
cases
a portion
in a chromosome
and
had
or third
relapses
disease
a change
of
resemblimig
in the
chromosomal
disease
that
Our patients
to
asked
about
in acute
can be investigated.
have
changes
in the
those
found
our
can a cell
apparently
live
in
2 surviving
line be
continues
yearst#{176}with
constitution
for
a large
acute
patients
maintained
to respond
more
than
proportion
chromosome
and
(as
of the
untreated
or in
the
In
cells
They
malignant
always
comicluded
cell
is omie of
earliest
phases
of marrow
a crucial
No.
having
second
karyotype
leukemia?
1) or
an
for
to
How
more
aneupboid
of
cells
question
genetic
constitution
control
mechanisms?
in Case
marrow
regardless
in the
develop
with
an abnormal
to homeostatic
of bomie
normal
constitution
thus
is, will they
7 months
the
to 4 months.
is present
leukemia,
during
remission,
47 to 65.
of the
and
of acute
made
aneuploid
up
of
were
patients,
from
hut
of
many
of 8 cases
restored,
observed
lengths
leukemia
study
All
ranging
originally
disorders,
During
employed.
of varying
abnormality,
association
observations
invarial)ly
was
numbers
the
remissions
alterations
similar
modal
studied,
after
a careful
serial
therapy
a different
remnarkable
hematobogic
remissions.3
cells
or the
hyperdiploid
reemerged
published
intervening
the
of
in which
of 46 in marrow
relapse,
can
which
a diversity
leukemia.
have
in children
of the
I)asic
with
in acute
co-workers
stem-cell
tient
of
as yet
group-namely,
of our three
cases,
a C group
chromosome,
which
terminate
Reisman
and
the
one
another
for
number
above-mentioned
overt
involving
or tetrasomy
Only
of
sign
poly-
autosome.
aberrant
that
of
a patieuit
2 extra
chromsomes
from fibroblast
cultures
no
in the
sign
with
marrow
karyotypes;
hyperdiploidy
with
a significant
shown
patients
no
of a D chromosome
The addition
all involving
diploid
five
shown
normal
showed
and
studies
14/ 14 patiemits
followed
with
cells
and
has
a C chromosome.
arms
a C group
the
She
of C group
chromosomes
of a C, monosomy,
trisomy,
involved
long
has
vera;
chromosomes
blood
cells
the
have
trisomy)
the
48
number.
date,
abnormalities
long arms
Kemp’
is polycythemia
amiemia,
chromosornal
that
cythemia
vera and 2/2 with thrombocythemia
had
1/3 patients
with myelofibrosis-myeloid
metaplasia
whose
findings,
marrow.
describing
report
Two
of the
patients
re-
be
long
which
If a pathan
4
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
796
ROWLEY,
ber,
then
it
sufficient
would
for the
On
the
other
( mongolism
seem
hand,
) with
may
have
acute
myebogenous
of
be
cent
aneupboid
of
congenital
reversil)ie
leukemia
57.
diagnosed
amid a platelet
A complete
months
on
the
child
in
remission
“usual”
for
Down’s
during
the
initial
examination
was
the
due
well
predisposition
characterizes
It
phase;
that
which
results
chromosome.
would
while
denote
normal,
but
The
still
considered.
ogous
pairs
missing
Cases
be
of chromosomes
identification
2 and
3
of
possible
1 and
at
present.
chromosome
is involved
in all three
cases
of aneuploidy
in acute
leukemia
this
probably
group.
results
It is also
from
possible
hemopoietic
alteration
tissue
are
in the number
decrease,
may
change
the
that
the
all
which
occur
technics.
does
not
hut
of part
in size
difference
of the
plus
number
4 of
balance
of the
the
C
group
whether
system
5
be
attending
identificatiomi
of the
C chromosome(s)
that
of chromosomes
one or more
chromosomes,
the
now
uncertainties
conceivable
for
abcells.
may
cases.
It is also worth
noting
involve
C group
chromosomes.’
responsible
a more
transform
between
known
homolin size between
ad-
duplicated
is
However,
of itself
autonomous
specific
It
of a
which
provide
to
cases,
or
of the cell.
chromosomes
could
may
also
radiation
C chromosomes
the
in their
deletion
3 of our
group
larger
genetic
related
virus,
agent
posanemia;
deletion
to abnormal
genes
located
on
of C group
in remisanemia
are
line
is
6 cases
or in the
stem
3
which
examined
example,
in
other
genetic
constitution
change
in the
C. Because
No.
21
the
aplastic
a different
that
noted
sideroachrestic
C chromosomes,
in Case
is not
or
cells
in group
of group
C chromosome
gross
that the variation
greater
than
the
shown
were
having
(for
34,400
marrow
chromosome
.32
a predisposition
summarized
above.
aneupboid
ol)servation
may
trisomy
on
relatively
insensitive
chromosome
number
agent
abnormalities
Patau#{176} has
exact
a stable
controllable,
of the
with
chromosomal
original
involve
chromosomes
jacent
the
was
Marrow
conditions
the
a
of
the
cent primitive
monomarrow
preparation
domie
of a chromosome
our current,
that an altered
partially
of others,
three
agent
significant
by
for
significance
cases
or loss
change,
milieu
All
on
Bone
not
one
to
life
count
therapy
idiopathic
aneuploidy
10,000.
age.
second,
initially
to alter
be reflected
in
gain
a neoplastic
propitious
the
acts
may
undetected
data
suggest
itself
considered
of
of
children
in acute
leukemia,4,”
reported
by others
and
A genetically
be
our
was
4 of the
a leukemogemiic
in the
without
3 years
21.
dissimilar,
the
to terminate
the 5 cases
is possible
of
syndrome
that
cell
than
chromosomes
thrombocythemia.
chemical
carcinogen)
This
altered
genome
not
was
day
and 33 per
in a direct
Karyotyping
“leukemic”
idiopathic
at
47
revealed
syndrome.
to chloramphenicol;
third,
JACOBSON
Down’s
tenth
blood
of less
remission
still
sion and had the standard
tnisomy
Our patients
are clinically
quite
sibly
is
child
the
white
count
hematobogic
and
line
with
One
examination
showed
40 per cent granulocytes
nuclear
cells.
The modal
chromosome
number
was
infants
7
instances.
ecchymoses,
blasts
cell
leukemia3#{176} suggests
imi rare
hepatospienomegaly,
36 per
stable
et al. ‘s report
transient
leukemia
with
a
AND
of leukemia.
Engel
and
1)asis
that
development
BLAISDELL
present
homeostatic
imi
the
same
that
many
In part,
in the
control
chromosomes.
by an increase
and
thus
disturb
C
of
Any
or a
the
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
CHROMOSOME
STUDIES
normal
homeostatic
vations
that
be
control
with
hematologic
the
aneuploidy
depends
could
malities
accumulation
from
many
of the
leukemia
case
publication
in patients
without
account
of which
the
terminate
in
Much
signs
of malignant
C
disorders
valuable
cases
to
acute
between
hematopoietic
reports.
obserseem
relationship
related
of similar
overt
for
chromosomes
possible
and
of more
the
would
of C group
disorders,
acute
obtained
observed
This
as duplications
determination
and
on the
be
of hemopoiesis.
as well
However,
group
797
PRELEUKEMIA
deletion
associated
leukemia.
IN
information
of chromosome
abnor-
neoplasia.
SUMMARY
All
Three
patients
with
different
3 patients
had abnormalities
cells.
Case
marrow
1 is
cells
a 23-year-old
contained
2 is a 62-year-old
his
bone
marrow
man
with
aplastic
45 chromosomes,
man
chromosome
obscure
hematologic
disorders
are
of chromosome
number
confined
who
cells
which
died
with
idiopathic
marrow
cells
contained
contained
to
missing
chromosomes
47
be
an
most
autosome.
while
chromosomes,
his
group
with
an
Case
3
most
extra
is
C
a
majority
cell
of
group
59-year-old
of
minority
bone
C. Case
anemia;
the
a stable
of
from
sideroachrestic
thrombocythemia;
46
one
of idiopathic
appeared
woman
with
anemia;
presented.
to marrow
bier
line
hone
had
48
chromosomes.
Although
many
disorders
ative
of the
have
aberration,
had
somal
anomaly
which
aneuploidy
clinical
that
but
favorable
milieu
frequent
occurrence
be
for
genetic
ing
balance
agent
action
of
a C group
result
of some
in leukemia
other
Es
de
presentate
natura
chromosomas
23 annos
le casos
obscur.
Omne
solmente
de
etate
con
some
de
aplastic.
the
is
the
these
chromogroup
not
of itself
may
provide
in
Because
in these
cases
of marrow
or more
C chromosomes
one
chromosome(s)
and
coupled
proportion
produce
a more
agent.
of hemopoiesis,
of
the
disormight
that
a change
with
a transform-
of individuals
in
than
group.
IN
INTERLINCUA
3 patientes
in Ic cellulas
does
genome
in a greater
be 3 patientes
anemia
line
transforming
on
chromosomal
SUMMARIO
which
of
patients.
stem
genes
chromosomal
None
patients,
C,
of the
control
some
4 of the
group
abnormalities
that
with
summarized.
In
in
alteration
homeostatic
involving
might
aneuploidy
the
postulated
for
are
aneuploid
this
of C group
it is further
responsible
others,
in all 3 of our
that
myelodysplastic-myeboprolifer-
5 cases
of leukemia.
a stable,
rather
with
a chromosome
occurred
It is postulated
by
evidence
involved
neopiasia,
patients
chromosomes,
reported
previously
patients
ders,
reported
normal
con
habeva
differente
medullari.
Le
majoritate
Caso
hematobogic
disordines
anormalitates
del
No.
de
rnmmeros
del
1 es tmn masculo
de
su celbulas
de
medulla
contineva
45 chromosomas,
i.e., un chromoscma
mancava
in gruppo
C.
Case No. 2 es un masculo
de 62 annos
de etate
qui moriva
de idiopathic
anemia
sideroachrestic.
Le majoritate
de su celbulas
de medulla
ossee
contineva
47
ossee
chromosomas,
qual pareva
i.e., ible habeva
esser un autosoma.
un chromosoma
supernumerari
Caso
No. 3 es tin femina
de
de gruppo
59 annos
de
C le
etate
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
798
ROWLEY,
con
thrombocythemia
medulla
idiopathic.
ossee
Ben
contine
que
46
mubtes
del
myeboprohiferative
de
iste
chromosomnatic
in le qual
gruppo
Es
que
neopbasia
se
sed
favorabibe
que,
plus
il
C
gruppo
de
in
be 1)alallcia
del
gruppo
C pote,
in beucemia
del
in
abtere
tin
plus
gruppos
regulation
genetic
grande
in
gruppo
C,
non
genoma
4,
be
i.e.,
be
produce
provide
in
iste
de
casos
del
be fre-
disordimies
de
hemopoiese
e que
o plure
chromo-
transformatori,
subjectos
plus
chromosomas
chromosomna
agente
per
un
Viste
homeostatic
de
altere
patientes.
C
tin
Ic
summarisate.
transformatori.
till
proportiomi
de
o plure
de
o
beucemia.
un
afficiente
be presentia
in
48.
es
de
del
gruppo
genes
in
que
alteres,
primordial
agente
un
del
in plus
pro le
alteration
somas
de
de
habeva
myebodyspbastic-
nostre
linea
stm cellulas
be tin
chromosoma
ommie
JACOBSON
cellubas
con
per
alteratiomi
anormabitates
postulate
respomisabile
es
iste
be action
es
casos
clinic
amieuploidic
tosto,
pro
occurrentia
medullari,
in
de
disordines
5
tin
occurreva
stabile
till
ambiente
quente
tin
aneupboidia
postulate
con
evidentia
concerneva
de
binea
reportate
manifestava
AND
be majoritate
normal,
previemente
patientes
anormalitate
patiemites
chromosomas
chromosomatic,
Nulle
que
tmn stabile
reportate
ha
aberration
Durante
chromosomas,
BLAISDELL
qtme
resultar
anetmpboidia
imi tin
chromosomnatic.
ACKNOWLEDGMENTS
We
wish
to
A.
Mendel.
(;er:ild
and
for
E.
Carsomi
make
mimaking
for
I)m’. Margot
the
following
LI.
Paul
available
the
and
special
Xg
Doyle
acknowledgmnents:
Miller.
1)100(1
and
NIrs.
muaterial
typing
and
Framices
To
Stanley
in
each
red
cell
Skozen
Drs.
Ernest
Beutler,
for
referring
the
Yachnin.
for
case;
to
Drs.
enzyme
Jamiies
E.
determuinations
invaluable
editorial
Fred
II.
patients
Katz,
reported
Bowmuami
amid
in
1;
Case
Paul
amid
to
assistance.
ADDENDUM
Skimi
cimltures
obtaimiecl.
No
group
14re’
obtained
Time
Case
miit’taphast’s
chromuos)mile
in
fromn
labeled
found
WS
No.
were
in
2 became
obtained
Case
No.
contamuim)ate(I
fromn
3.
More
Cas’
amid
No.
recent
2:
no
onl
studies
im,itotic
one
on
cells
were
late-labelimig
Case
No.
C
3
are
in
Laneel.
REFERENCES
1. Samidberg.
Y..
A.
and
some
A..
Ishihara.
Crosswhite.
differences
kemiiias.
‘F..
L.
amnong
Ann.
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the
Y. Acad.
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Kikuchi.
11.:
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Sci.
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leim-
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Reismami,
L.
W.
li..
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Mitani.
NV.:
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stemii
from
lines
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Zuel-
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of
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as
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the
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preacute
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amid
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himmuan
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Myeloproliferative
other
svn-
ats’pical
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acute
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bomiib
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dromne
radiat:on
of
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observation
aneuploidy
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From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
1966 27: 782-799
Chromosome Studies in Preleukemia: I. Aneuploidy of Group C
Chromosomes in Three Patients
JANET D. ROWLEY, RICHARD K. BLAISDELL, LEON O. JACOBSON, Judith Mikuta, Rachel Byrne and
Lona Shepley
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