From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
Multiple
Chromosomal
Acute
Granulocytic
Down’s
Study
By
Aberrations
Leukemia
Syndrome
A.
KIosSoGLou,
With
1930,
N
in
a
1963,
further
acute
leukemia
et
in
It
was
until
conclusively
few
G
later,
in
1960,
a
investigations
as
normal
number
the
ment
of
discussed
classical
stimulated.
In
found
other
conditions.
Recently,
we
syndrome
merous
viously
twin
in
From
and
the
Aided
Submitted
Down’s
had
and
the
acute
in
the
of
with
from
U.S.P.H.S.
funds
Nov.
12,
1963;
accepted
association
with
chronic
described.4m
in
leukemia
As
human
no
additional
occurring
cases.
in
However,
anomalies
to the
Down’s
in
was found
chromosomal
other
in cases
comple-
in
recent
syndrome
as
well
studying
a 4-year-old
the
Pratt
Tufts
a twin
patient,
sets
some
of twins
presence
Jan.
normal.
chromosomal
England
School
with
was
aras
in
Down’s
Nu-
of them
never
pre(with
one
affected
of
Clinic-New
Univemity
Grant
#CY-4168.
for publication
boy
sister
a
neoplas-
McKusick57
and
Laboratory,
human
and
in
Medicine,
a constant
Down’s
each
of
of
A
classical
studies,76”7’90’#{176}4
of
leukemia;
family;
as 46.
in
in this
of two
Research
of
now
Eggen22
aberrations
the occurrence
the
Blood
Department
cases
Hamerton2’
the
aberrations
some
aberrations
opportunity
and
was
chromosomal
in addition
granulocytic
the
in
cases
chromosomal
described;
set)
50
of
disease.
non-leukemic
syndrome.
chromosomal
of
Stewart
chromosomes
example
a specific
chromosomal
with
of
Ford
described
first
with
possible
were
leuand
incidence
1958,
a total
of human
anomaly,
compared
increased
and
Gautier5
chromosome),
further
acute
1947
.
found
Levan88
and
studies,’#{176}’54’73’93’95’#{176}8
a variety
of
of acute
leukemia
and
mongolism,
ticles
and
chromosomal
anomalies
syndrome,
had
(Philadelphia
of
were
chromosomal
Tjio
syndrome,
specific
example
of
) Between
leukemia.
associated
leukemia
diseases
tic
Stewart83
with
Turpin
Down’s
first
dying
of leukemia,
18 were
associated
or nearly
20 times
the
incidence
cent
1961,
the
aberration
granulocytic
result,
per
that
Lejeune,
trisomy
chromosomal
In
1956,
established
years
21
children
NIITUS
Sheehan
syndrome
the
demonstrating
(2.6
associated
not
the
( Down’s
677
By
normals).
syndrome
of Carol
syndrome.7”’#{176}”5’48’49’6#{176}’65’M7’#{176}’In
syndrome
in
Down’s
J.
\V.
ROSENBAUM,
Cannon’#{176} reported
of
Tendency
DAMESHEK
assistance
mongolism
appeared
Down’s
that
Down’s
leukemia
of
WILLIAM
technical
and
case
reports
al.TM5 reported
with
the
Brewster
kemia
Twinning
H.
ERNEST
AND
I
and
of a Family
with a Possible
to Nondisjunction
KosMAs
.
in a Patient
with
Associated
with
of
aberra-
Ce’nter
Boston,
Medicine,
Hospital,
Mass.
7, 1964.
134
BLOOD,
VOL.
24, No.
2
(AuGusT),
1964
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MULTIPLE
CHROMOSOMAL
tions
in
occasion
the
for
135
ABERRATIONS
mother,
maternal
presentation
of
grandmother
this report.
CASE
A
4-year-old
Hospital
of
white
on
boy
January
3 weeks’
with
was
53
years
was
no
history
the
and
the
His
twin
The
old
end
of
child
was
said
prior
per
to
hut
One
of
patient
fetal
the
to
the
has
continued
have
had
pallor
and
since
Floating
was
was
birth.
spoke
a
referred
He
jaundice
the
walked
a few
words.
small
amount
of
to
hospital,
studies
noted
subsided.
lighter
with
fluid
penicillin
or
was
blood
but
( hemoglobin
administration
of
and
taken
was
months,
kerosene
splenomegaly
examination
further
15-16
therapy
iron
There
was
had
anemia
oral
of
present.
at
only
responded
from
for
to
with
our
established
the
birth.
X-ray
jaundice
hospitalization,
improve
to
after
weeks
a physician,
patient’s
One
slight
health
36
father,
the
labor.
birth,
days
pneumonitis
to
admission
except
no
at
given.
x-ray
the
the
and
Except
exposure.
ingested
noted
and
blood
and
bone
the
marrow
therapy.
age
3. He
of
three
for
the
There
had
injections
one
was
been
of
maternal
no
immunized
DPT
x-ray
history
of
with
vaccine.
three
Sabin
for
I
pelvimetry
exposure
to
injections
and
III
vac-
prenatally,
toxic
drugs
or
he
chemicals
kerosene.
Hi.rtory
Family
The
father,
both
were
them
alive:
and
“croup”
vaccine
also
had
age
(1)
well;
(3)
M.,
propositus,
was
and
N.
twins,
of Italian
well.
M.,
They
male,
(a)
R.
of a prolonged
the diagnosis
diffuse
C.
57,
living
product
3 with
revealed
atrophy
female,
male,
age
the
mother,
seven
children,
age
22,
living
and
M.,
male
age
19,
45,
of English-Irish
including
well;
two
(2)
living
M.
and
sets
M.,
well;
extraction;
of
female,
(b)
twins,
age
X.
M.,
six
21,
of
living
female,
was
labor
with
severe
anoxia.
She had been
institutionalized
at
of chronic
brain
disease;
she died
at the age of 17. Autopsy
of
age
extraction,
had
the
14,
4 and
cerebellum,
living
(b)
K.
hippocampi,
and
well;
M.,
female,
cerebral
(5)
hemispheres
(Second
age
4,
set
living
of
and
and
thalamus.
twins:)
well.
(a)
Maternal
mother,
69 years
old, living
and well.
There
was no family
history
of cancer,
heart,
lung or kidney
disease,
culosis,
leukemia
or Down’s
syndrome
in the previous
three
generations.
prior history
of either
twinning
or mental
retardation
was obtained,
except
P.
M.,
grand-
diabetes,
tuberIn addition,
no
as noted
above
1).
Physical
Physical
Examination
examination
revealed
an
irritable,
stigmata
of monogolism.
The temperature
weight
28#{189}pounds,
height
37
inches.
expiratory
rales and wheezes
were
noted
was
the
splenomegaly
after
The
of
or
good
During
The
time
At
18
swallowed
failed
before
the
in
and
he
at
delivered
pounds.
position.
pneumonitis.
anemia
child
had
were
had
(fig.
are
Boston
anemia
been
41/,
pregnancy
hospital
and
leukemia
poliomyelitis
cines
(4)
ascertain
discovered.
week
The
Salk
the
age
siblings
His’tory
The
of
to
admission
the
acute
preparations.
Past
the
admitted
malaise,
having
was
old
during
successfully
) was
cent
transfusions.
diagnosis
to
years
bleeding
developed
terramycin,
41
or
from
normal
toilet-trained
weeks
Cm.
7.2
was
of fever,
pregnancy,
Birth
weight
mother
discharged
was
subsequently
and
the
infection
was
been
Three
and
syndrome
evaluation
a twin
labor.
pregnancy
sister
not
and
of
patient
had
of
duration.
He was the product
of
gestation
following
a 2-hour
near
for
one
REPORT
Down’s
1963,
28,
and
a grade
II
hemic
systolic
murmur
over
pale
was
There
at
and
103
weak
F.,
child
pulse
was
no
140,
icterus.
the
base
of the
left
the
apex
of
heart.
the
with
all
the
respirations
Rhonchi
lung
The
and
posteriorly.
liver
classical
40/mm.,
a
few
There
and
spleen
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
136
KIOSSOGLOU,
Age4
Age4
Age 14
Age
ROSENBAUM,
19
/
DAMESHEK
MM
Age 21
Deceased
Age
AND
MITUS
NM
Age 22
7
\
Deceased
-
Not
Studied
Nondisjunction
0
Normal
Propositus
Down’s
Broin
Congenital
Fig.
were
palpable
small
palpable
3.5
examination
was
Laboratory
The
(table
using
cm.
lymph
Atrophy1
and
within
11
in
(See
cm.
different
below
Not
Chromosomol
Abberrotions
Studied.
chromosomal
their
study.
respective
axillary
costal
and
margins.
femoral
There
regions.
were
Neurologic
limits.
Table
methods
-
submandibular,
1)
mean
average
polymorphonuclear
2). Sex chromatin
(Barr
bodies)
two
Multiple
tree:
the
normal
A.G.L.,
Deceased
1.-Family
nodes
Data
Syndrome,
on
two
lobe
count
studies
occasions;
was
were
both
1.43
performed
were
negative
(normal
2.10
on
the
for
female
±
buccal
.21
)43
mucosa
characteris-
tics.47’78
Bone
the
a
marrow
cells
fine
were
aspiration
primitive
chromatin
light blue
azurophilic
megakaryocytes
and
network
near
granules
were
the
yielded
in
only
appearance.
and
the
Their
amounts
round
of material.
or
slightly
Over
indented
80
per
nuclei
cent
of
showed
nucleoli.
The
moderate
amount
of cytoplasm
stained
of the nucleus
the cytoplasm
was
pink.
A few
primitive
some
of these
cells
were
peroxidase
positive.
No
erythroid
elements
were scanty. A bone marrow
biopsy
was
2-4
indentation
were
noted;
seen;
scanty
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
CHROMOSOMAL
137
ABERRATIONS
Table
1.-Laboratory
Data
on
the
Propositus
Blood
Chemistry
Hemoglobin
Hematocrit
3.3 Gm./100
ml.
Total
serum
Albumin
Globulin
Serum
paper
Albumin
15%
Red blood
Platelets
1.62 M
cells
10,000/cu.
5.8%
8,800/cu.
Reticulocytes
White
blood cells
Differential:
Myeloblasts
Eosinophilic
mm.
mm.
Alpha,
Alpha
45
0.5
myelocytes
Uric acid
Serum
alkaline
Serum
iron
Iron
binding
SGOT
8
Monocytes
cells
0.5
3
cells
phosphatase:
11.7%
13.3%
11.7%
13.0%
of serum
proteins:
within
normal
limits
capacity
SG 1021-no
occasional
albumin,
122
score
17 mg. %
6.0mg.
%
3.1 BU
phosphatase
SGPT
Urine:
WBC
2/100
%
%
50.3%
globulin
globulin
BUN
9
20
%
electrophoresis:
16
Band
form
polymorphs
Segmented
polymorphs
Small
lymphocytes
Large
lymphocytes
Atypical
lymphocytes
Reticulum
6.0 Gm.
3.7 Gm.
2.3 Gm.
Beta globulin
Gamma
globulin
Immunoelectrophoresis
Metamyelocytes
“Basket”
cells
Nucleated
red
Leukocyte
alkaline
proteins
150 zg./100
9 jg./100
52 units
13 units
sugar
or
hyaline
cast
ml.
ml.
(normal
15-55)
Table
2.-Polymorphonuclear
Members
Lobe
Family
of the
Count
(100
on the Propositus
Cells
Counted)#{176}
and
Eight
Mean
Lobe
Count
Age
1 Lobe
(years)
Father
57
Mother
45
P.M.f
K. M.
C. M.
4
4
R. M.
14
19
M.
M.
21
N.
NI.
22
(a)
2/9/63
(b)
2/28/63
2 Lobes
3 Lobes
4 Lobes
5 Lobes
25
27
65
30
43
19
18
35
41
28
39
39
51
52
31
27
6
22
14
23
27
9
5
1
8
4
0
2.24
0
2.10
0
1
1.43
2.11
0
1.79
5
2
2.20
2
1
2.16
40
49
36
36
21
14
3
1
0
1.87
0
1.67
23
37
29
10
1
2.29
Grandmother
(maternal)
69
#{176}All
subjects
were
f Four
hundred
myelocyte
level.
confirmatory
X-rays
survey
Hospital
The
of
the
showed
showed
in good
cells
diagnosis
an
no
at
health
time
of
test.
counted-propositus---blast
of
infiltration
acute
in
abnormalities.
the
excluded.
form
leukemia,
left
lung
Electrocardiogram
of
probably
base,
a
and
was
within
the
Count
started
granulocytic
pneumatocele.
normal
at
variety.
A
long
bone
limits.
Course
hospital
course
was
characterized
by
repeated
episodes
of
pneumonitis,
otitis
media
and urinary
tract infection,
which
were
treated,
at various
times,
with penicillin,
streptomycin,
sulfisoxazole
(Gantrisin)
and
nitrofurazone
(Furadantin).
For the leukemia,
6mercaptopurine
(6-MP)
2.5 mg./Kg./day
was used
initially.
A week
later,
prednisone,
40 mg/day
was added
because
of severe
bleeding
episodes.
After three
weeks
of therapy,
these
were
discontinued
and Vincristine#{176} therapy
was then
initiated
in a dosage
of 1.5
#{176}An
isomer
of the
Madagascar
periwinkle
(Vinca
Roses
Linn).
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
138
KIOSSOGLOU,
Table
3.-Modal
Number
of
Percentage
Number
of Chromosomes
42
28
Chromosomes,
Distribution
47
A.
ROSENBAUM,
48
Counted
on
49
January
to
51
0
7
0
0
1
46
Percentage
0
11.3
0
0
1.6
74.2
B.
5
26
Percentage
hypertetraploid
cell
not
Weeks
2
10.0
8
1
3.4
1
3.4
included
in
of
Weeks
the
Cells
and
52
53
99
7
Total
1
P
11.3
1.6
1.6
100%
0
0
1
5.0
0
0
20
100%
1
3.4
0
0
0
0
29
100%
16
80.0
of
chemotherapy
0
0
23
79.5
counted
62
chetherapy
1
5.0
1963-After
1
3.4
was
5
0
0
March
2
6.9
cells
1963-After
0
0
C.
Counted
5The
March
0
0
DAMESHEK
ch,,otherapy
Countedcells
Countedcells
Percentage
AND
Propositus
50
1963-Prior
MITUS
cells
and
the
percentage.
mg/week.
Numerous
blood
transfusions
were given
during
the whole
course.
After
5 and
again
after 8 weeks
of therapy,
bone
marrow
examinations
revealed
no essential
change.
The white
cell count
was
still
high
(18,000
cu. mm.)
with 70 per cent
of myeloblasts.
The child died at home
14 weeks
after
the original
admission.
No autopsy
was
performed.
CHROMOSOMAL
STUDIES
Methods
Peripheral
blood
et al.,64 with
were
performed
combined
slight
cultures
were
modifications.
according
to
Denver1
and
performed
by
the
method
Direct
bone
marrow
the
method
used
in
Patau#{176}8system
of
Moorhead
chromosomal
this
laboratory.44
of nomenclature
was
studies
The
used.
Results
Propositus:
On
leukemic
therapy
A
of
total
The
modal
January
and
63
28,
processed
of
cell.
had
cells
51 chromosomes;
had 50, 53 and
7 cells
March
5,
bone
method.
A
total
to
52
micrographed.
from
42
5 and
cells counted
for treatment)
with
and
1963,
The
20
3 with
A.
Analysis
autosomal
and
modal
52
47
exhibited
47
respectively.
51 and
of
and
three
B. two
one with
with
cells
again
52 chromosomes
January
28,
sex chromosomes
to
The
53
5 and
the
anti-
shown
chemo-
same
direct
counted
and
53 chromosomes
line
modal
photoand
on
both
number,
in table
Karyograms
50, 5 with
51,
51 chromosomes,
cells
three
of
the
cell
The
occa-
46
8 weeks
predominant
respectively
an
remaining
by
were
49 to
1963:
the
chromosomal
(figs.
2, 3 and 4).
with
chromoosmes;
processed
plates
from
47, 1 with
containing
prior
photomicrographed.
to
and
after
1963,
were
29 metaphase
number
ranged
chromosomes
and
from
chromosomes;
respectively.
26,
aspirations
on: A. 15 cells:
53 chromosomes;
cells:
March
ranged
cells
aspirated
method.
counted
March
26 contained
51 chromosomes.
and their percentage
distribution
are
and B and C (during
treatment).
March
formed
had
99 chromosomes
marrow
of
Seven
was
direct
were
chromosomes
hypertetraploid
marrow
the
figures
sional
On
bone
by
metaphase
number
therapy,
1963,
the
3: A (bewere
per-
5 with
52 and 1
and
C. four
(table
aberrations
4).
involved
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
CHROMOSOMAL
a. Autosomal
The
Aberrations
autosomal
variable
abncrmalities
involvement
47
of
Chromosomes
( classical
definitely
enlarged
( 2 ) orderly
( figs.
cells
stant
All
),
(3
as
The
well
presence
C,
cells
of these
or
the
chromosomes,
chromosomes,40’71’
of acentric
trisomic
)
the
in
in
3 and
except
for
a
a marked
the
of
be
karyotyped
and
the
)
(4
B,
C,
con-
and
chromatid
satellite
to
above),
karyotyped
11
4),
of
found.
G 21
leukemic
(see
all
10
3 and
4).
were
appeared
for
exhibited
trisomy
chromosomes
fragments
with
detected.
C 21
(figs.
trisomy
of
D series,
representing
regular
double)
autosomal
and
chromosomes
were
probably
(1)
E 17-18
F,
were
three
chromosomes
cells,
involving
constriction
the
Ph1
by:
occasional
remaining
secondary
and
as
n the
series.
karyotyped
These
(single
monosomies
Inconstant
E
( tetrasomy
or pentasomy
) constant
F 19-20
trisomy
was in the F 19 series
( figs.
polysomy
4
which
we beleved
D 13-15
triscmies
series,
No
characterized
G 22
and
.
Line:
3 and
constant
C,
of the
satellites.
were
cells
B,
) , ( fig. 2 ) One
Chromosomes
population,
were
the
Line:
G 21 trisomy
50-53
139
ABERRATIONS
E
break,
a
association,24’79
of
normal
configura-
tion.
1). Sex
Chromosomal
The
The
XY
configuration
variation
In
all
of
some
abnormal,
and
The
Family
Chromosome
and
shape
of
March
of
and
were
the
trisomies
and
and
arms
D 13-15
1963:
in
table
mother,
propositus.
of
6.
an
(both
(single
were
or
found
to
pattern,
occasional
sister
were
cells
are
shown
cells
on
the
in
table
eight
The
The
5.
members
of
and/or
structural
aberrations
M.)
and the maternal
grand-
(M.
characterized
reciprocal
tetrasomy
parents,
siblings
and
peripheral
blood.
of
karyotyped
Numerical
older
These
the
culture
counted
findings
pseudodiploid
occasional
26,
as G 22 tetrasomy
on
short-term
chromosomes
shown
in
of the
long
isochromosome.
performed
using
structural
are
found
mother
an
its
limits.8
X chromo-
4).
March
as well
remained
analyses
family
3 and
5 and
the
for
normal.
normal
chromosomes,
isochromosome
(figs.
)46
was
within
Analysis
number
numerical
chromosomes
was
50-53
an
G 21 trisomies
grandmother,
modal
47
Y chromosome
possibly
X chromosome
Chromosome
maternal
containing
the
containing
and
Analyses
persist.
were
being
F 19-20
cells
of
cells
in size
C.
double),
the
length
karypotyped
identical
B
in the
in the
the
was
arms
Aberrations
by
increased
translocations,
involving
the
and
aneuploidy,
monosomies,
chromosomes
of
the
A-G
series.
Normal
found
younger
The
modal
in
the
numbers
remaining
brother
X chromosome
and
and
five
sister,
in
and
the
regular
members
eight
twin
chromosome
of
sister
members
the
family:
configurations
father,
of the
propositus.
of
family
the
older
was
found
were
brother,
to
be
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
140
KIOSSOGLOU,
ROSENBAUM,
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AND
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From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
CHROMOSOMAL
141
ABERRATIONS
A
ii’
%%
Al
AZ
U U
C6
C7
D13
D14
X
21
F19
FZO
A3
H
C8
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ClO
Cli
Ci2
#{163}16
#{163}17
ea
II
D15
#{163}18
)
41
IA
022
GZI
Trisomy
Fig.
2.-P.
M.
(propositus):
Bone
phase
plate
containing
47 chromosomes.
sociation.
Karyotype
of the plate
is
XY configuration
is normal.
marrow
The
shown
XY
preparation,
arrow
below.
direct
method.
points
to a D-G satellite
C 21 trisomy
is present.
Meta-
asThe
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
142
XIOSSOGLOU,
MITITS
AND
DAMESHEK
1141t4i
,
*
ROSENBAUM,
11
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D15
D14
13-15
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E17
E18
Trisomy
AA
* t
GZI
F20
F19
19-20
II
022
TrisornyTetrasomy
Trisomy
?
Fig.
3.-P.
M.
(propositus):
Bone
marrow
preparation,
direct
phase
plate
containing
51 chromosomes.
Karyotype
of the plate
D 13-15,
F 19-20,
and C 21 trisomies,
as well
as C 22 tetrasomy
sex chromosomes
are represented
by an iso-X,Y
configuration.
entirely
the
normal.
father,
one
Satellite
nent
(N.M.
in
In most
of the cells
of the G 21 chromosomes
association
the
and
grandmother,
R.M.).
of
the
studied
chromosomes
mother,
of the
exhibited
of
older
the
sister
entire
(M.
and
M.)
Y
method.
Meta-
is shown
below.
are
present.
family,
enlarged
D
Iso-X,
The
excepting
satellites.
C series
and
was
the
promibrothers
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
CHROMOSOMAL
ABERRATIONS
143
0
*
S
IflIU$$
C6
C7
D13
C8
D14
C9
D15
D13-15
Double
u
do
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F
Fig.
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F19
F20
19-2
0 trisomy
D 13-15
are
M.
4.-P.
plate
double
(propositus):
chromosomes
are
Bone
52
trisomy,
Note
022
Trisomy
containing
present.
021
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the
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enlarged
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in
by an iso-X,Y
Tetrasomy
trisomies,
one of the
configuration.
of
?Iso-X,
Y
direct
method.
Metaplate
is shown
below.
as well
as C 22 tetrasomy
C 21 chromosomes.
The
sex
the
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
144
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ROSENBAUM,
MITUS
AND
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From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
CHROMOSOMAL
6.-Numerical
Table
145
ABERRATIONS
and
Eight
Structural
Members
Affected
No. of
KaryoName
No. of
Chromosomes
types
Father
2/9/63
3
Mother
2
46
2/15/63
1
47
1
47
2/26/63
A
II
Chromosome
of the
Series
According
Patau
System
C
D
Findings
on
Family
to the Combined
of Nomenclature
E
F
G
46
Denver
R2marks
and
normal
(XY)
T
1
45
2
45
1
45t
8
1
1
46
E 18
M
M
M
T
T
T
48
51
53
M
T
T-T-T
T-T
T
N.M.
2
D 15 monosomy
C 6 monoaomy
B5 and G21
trisomies
C6 and E16
mono-
and
E 18 trisomies
A 1-3,
C 6, F 20
Te-T
46
46
sional
2/28/63
(XY).
occa-
chromatid
and
normal
46
trisomies
tetrasomy
F 19
normal
brother
1
(XX)
trisomy
and
older
46
somies
normal
46 (XX)
B 5 and
F 19 trisomies
B5,
ClO,
Cli,
E16
T
T-T
Conclusions
constitution
normal
46
A2
trisomy
T
and
gap
46
break
(XY)
plus
two
acentric
fragments
normal
46 (XY).
double
G-G and
D.G
and
quad.
46
ruple
D-D
satellite
as-
sociation
MM.
1
45
older
sister
2/25/63
1
46
3
1
46
47
R.M.
younger
M
M
M
1
47
3
46
T
T
M
T
T-T
T
B 5 and
C 6 monosomies
and
G 21 trisomy
pseudodiploid
(D 15 monosomy
and
E18
trisomy
normal
46 (XX)
A 3 monosomy
and
C 11.
D13,
D14
trisomles
C 12 trlsomy
T
normal
satellite
6/1/63
one
CM.
younger
46
1
E16
46
D-G
configuration
quadruple
association
(XY);
brother
and
in
cell
normal
46
consititution
(XX)
sister
6/1/63
KM.
twin
4
46
1
normal
(XX)
sister
configuration
46
2/9/63
G. M.
maternal
grandmother
4
45
46
6/1/63
1
47
1
Cl
M
C 9 monosomy
normal
(XX)
T
T-T-T
F 19 trisomy
C8.
Cli.
C12.
T
T
E16
M = monosomy;
5One
of the
sessed
enlarged
tForty-flve
T
=
trsomy;
Te
G 21 chromosomes
satellites,
except
chromosomes
location).
Forty-seven
chromosomes
E 16/D
translocations).
in
the
carrying
carrying
karyotype
46
D13
and
trisomies
tetrasomy.
most
father.
genetic
genetic
of
the
karyotyped
material
material
cells
of
of
of
the
members
46
chromosomes
(unusual
49
chromosomes
(two
of
the
C 7/G
unusual:
family
21
C 7/D
postrans.
and
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146
KIOSSOCLOU,
ROSENBAUM,
MITUS
AND
DAMESHEK
0
I
lic II)
Al
Trisomy
(I)
C6
Trisomy
1
D13
1111
119
Tetrasomy
(U
II
II
A3
B4
B5
AZ
Trisomy
Trisomy
(I
(I
C7
C8
II
)$
D14
D15
c( n
C9
dO
III
Trisomy
Fig.
5.-M.
M. (mother
of the
plate
containing
53 chromosomes.
sociation.
Karvotype
of the
plate
trisomies,
as well as F 19 tetrasomy
CII
U
C12
11
11
E16
E17
E18
021
022
#{149}$I1
F20
1,
4’
(1
xx
propositus):
Peripheral
blood
culture.
Metaphase
The
arrow
points
to a double
D-G
satellite
asis shown
below.
A 1, A 2, A 3, C 6 and
F 20
are present.
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MULTIPLE
CHEOMOSOMAL
147
ABERRATIONS
4
3
-3
1
*____
IC
II
06
Ii
Dl
F1)
Fig.
07
6.-N.
C8
II
1*
D14
D15
#{149}
is
Metaphase
and
D-G,
is shown
III U11
U
C9
010
U
E16
as
as
F2C
G21
M. (elder
brother
of the
propositus):
plate
containing
46 chromosomes.
Arrows
as well
as quadruple
D-D
satellite
associations.
below
(normal
karyogram).
u
Cli
H
C12
$1
E17
#{149}.
E18
(
G22
Peripheral
blood
culture.
point
to two
double
C-C
Karyotype
of the plate
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148
KIOSSOGLOU,
ROSENBAUM,
MITUS
AND
DAMESHEK
C
)‘
42
84
11(1111112
C6
C8
UsIa
C9
ClO
?Thsomy
#{149}1
D13
Trisomy
D14
Trisorny
D15
B5
C12
II
E16
Trisomy
E17
o
E18
1h
F19
F20
G21
G22
xx
Fig.
7.-M.
M. (elder
sister
of the propositus):
Peripheral
blood
culture.
Metaphase
plate
containing
47 chromosomes.
The
arrows
point
to two
unusual
D/C
and E/D
translocations.
Karyotype
of the plate
is shown
below.
A 3 monosomy,
as
well
as C 11 trisomy,
D 13-15
double
and
E 16 trisomies
are
present.
In
final
analysis,
the 47 chromosomes
are carrying
genetic
material
of 49 chromosomes,
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IULTIPLE
CIIIIOMOSOMAL
149
ABERRATIONS
‘I
IL
P
LI
Laj.L
07
C6
CO
C9
h1I*#{248}
Dl3
,
ias
F19
0114
012
ClO
a,
Dl
is
E18
El?
E16
IA
(1
022
G21
F20
Trisorny
Fig.
8.-Grandmother
Metaphase
low.
plate
F 19 trisomy
containing
is present.
(maternal)
47
of the
chromosomes.
propositus:
Karyotype
Peripheral
of
the
blood
plate
culture.
is shown
be-
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150
iuosociou,
Analytical
members
The
findings
ir normal
the family
may be
of
polymorphonuclear
counts
and
seen
abnormal
in table
lobe
count
mean
on members
of the
ROSENBAUM,
family
were
MITUS
AND
DAMESHEK
karyotyped
cells
of all eight
6 and in figures
5, 6, 7 and 8.
( table
2 ) and
normal
within
the
differential
range.43
DiscusSioN
The
increased
incidence
stressed
by many
yet to be clarified.
sibships.
an
Recently,
increased
of
acute
leukemia
in
authors,1848’50’#{176}5’76’85 but
Mongolism
and
leukemia
in
a
incidence
sibships.
In
some
prenatal
in
origin.
national
cooperative
of leukemia
cases
leukemia
In
other
Down’s
syndrome
the nature
are known
of
survey
has
by
reported
and
Down’s
was
congenital,7’48’49’53’#{176}7’7#{176}aid
instances
it
syndrome
occurred
been
this association
to occur
in the
was
has
same
Miller,63
found
months
or
among
perhaps
years
after
birth.39’#{176}’73’70’87’93’95
According
to
childhood
many
is that
leukemia
no more
are
than
authors,9’2#{176} the
of
the
acute
much
less common
10 per cent
of all
hand,
a far
higher
occurs
than
in
infrequently
incidence
the
and
cases.
of acute
childhood
most
common
type
variety.
AGL
lymphoblastic
in
leukemia
and
between
them
probably
In Down’s
syndrome,
granulocytic
general,
differentiation
of
account
on the
for
other
leukemia,9’49’54’6073’768193’95
but
it
between
in
monocytic
the
should
be
various
stated
forms
may
that
not
be
diffi-
cult.9’20’73’#{176}5
The
problem
syndrome
is further
with
follow-up
studies,
their
hematologic
served
one
complicated
a leukemia-like
some
of these
picture
and
such
by the
picture
example.
in
occasional
patients
develop
no evidence
of
A case
of
association
newborn
Lahey
et
and
of Down’s
young
complete
leukemia.74’8’
infants.
On
normalization
We
have
al.5#{176}
probably
belongs
of
obto
Originally,
many
chromosomal
investigators
aberrations
were
in
changes
of the modal
been
described,39’76’77’90
cases
number
and,
unable
of
to
demonstrate
any
AGL.76’90#{176}4 Nevertheless,
in the form
more
recently,
specific
numerical
of aneuploidy
or polyploidy
a variety
of chromosomal
have
anom-
alies
has been
found.34’39’54’7376’9395’#{176}7
In 1961,
Kinlough
and
Robson42
scribed
two cases
of AGL
with
an extra
chromosome
similar
in size with
D 13-15
of
the
category.
same
group.
medium
four
of
chromosomal
the
anomaly
the
Ross
G 21
and
the
cases
of
(C
AGL,
6-12)
In
this
similar
to
C 6-12
autosomal
Atkins,73
found
who
and
laboratory,
of
that
we
been
have
had
trisomic
the
patients
by
the
range
described34’39’93’95’97
C 21
two
in
Kinlough
in
Down’s
opportunity
with
AGL,
and
Robson42
synto study
one
having
and
four
trisomy.45
described
ranged
chromosome
has
in
described
a modal
number
extra
non-mongoloid
AGL
number
in the G 21-22
series.
This
In a similar
case reported
modal
an
series
non-mongoloid34’97
pattern
trisomy,
acrocentrics
disjunction.
girl,
ten
children.39’95
the
showing
other
submetacentric
out
drome
In
dethe
from
in a case
of
49
was attributed
by Lejeune
47
to
of Down’s
chromosomes
54
et
with
syndrome
with
seven
small
to double
mitotic
nonal.54 of a 26-month-old
chromosomes,
suggesting
a
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
clonal
CHROMOSOMAL
evolution
of
were
involved
ries
case
with
somy,
modal
one
trisomy
were
Initial
53
in
The
G,
As
to
extra
chromosomes
and
A 3,
the
for
highly
A number
chromosomal
the
association
a
constitution
or
potential
possible
resulting
malignancy.
an
many
may
in
for
the
size
the
of
this
axis.46
A 3 and
prob-
the
for
the
normal
presence
propositus
but
abnormal,
were
between
at
exists
development
a
It
neoplasia.
As
to
the
Some
material
cases
of leukemia
of certain
hemic
chronic
granulocytic
leukemia
be
appear
cells.
a first
to
This
where
a result
erratic
an
occurs
beyond
some,
a
requisite
Thus,
be characterized
seems
to be
a specific
leu-
doubt,
the
leukemia,
factors
final
by
chromosomal
with
and
in
the
aber-
persons
exogenous
of
aberrafirst-the
predisposition
to
clone
neoplasia.72’85
reasonable
mechanisms
and
chromosomal
chromosomal
process.
have
spontrans-
chromosomal
which
seems
of
aberrant
for
and
to
pathogenic
in
an
of
demonstrable
may
factors
may
as
leukemic
constitution
as
expressivity,
between
of
constitutional
mutation,
time
sex-linked,
to a neoplastic
with
leukemia
this
change.8#{176}
a correlation
cell
well
a predisposing
post-natally
specific
as
or
containing
representative
perhaps
of
as
anomalies,28
autosomal
cell
sex
incidence
chromosome
susceptible
the
be
between
increased
trisomy,26’31’51’62’99
sex
a
or
that
clear
association
an
whether
to be
consder
an
G 21
pre-
may
chromosomal
for
in
longitudinal
advanced
addition,
Thus,
either
relationships
the
that
in
representing
of
reported
abnormalities,
chromosomal
that
and
be
and
appears
it is not
the
C 7 pair
cells
with
potential.
mutation
one
known,
however,
abnormal
These
configuration
possessing
or
the
constantly
misdivisoin
normal
autosomal
acquired
or
Although
of
simulating
trisomic
In
associated
neoplastic
Thus,
constitution
X,
the
also
oc-
nondisjunctions.
mitotic
are
leukemic
leukemia.
combined
induced
formation.
are
and
described.
have
the
than
could
the
three
unlikely.
of
taneous
rations
in
to
respectively).
) found
cells
of the
42
constitution
mitotic
secondary
leukemic
member
of
to
of therapy.
polysomies
arms
a
explanations
defects
genetic
kemia
C 7, one
anomalies
sex
tions
long
to
these
cent
genetic
47
antileukemic
and
on
per
to multiple
of authors3’41’52’59’62’9#{176} have
chromosomal
cells
and
line
79.3
as a result
rather
the
chromosome
considered
to
G 21
from
of
chromosomes
cell
hereditary
transverse
Other
iso-X
been
A 3 tetraand
containing
53
and
80
due
the
due
is that
chromosome.
seem
latter
S weeks
to
predominant
probably
was
49
( 74.2,
to occur
for
along
have
the
monosomy
cells
5 and
from
presumed
were
this
possibility
the
F 19
revealed
( trisomies
series
monosomic
of
the
isochromosome
chromosome
x
In
series,
after
ranging
demonstrated
D
chromosome
ably
case,
The
of
be
Another
chromosomes.
C
analysis
51 chromosomes
restoration
the
49
the
present
cells
could
F,
and
respectively.
contained
no
the
the
revealed
chromosomes
patient
#{149}
in
Subsequent
chemotherapy
Thus,
of 47
Chromosomes
of the C, D, C, and F seRecently,
Vincent
et al.93 also reported
a
present.
analysis,
casions
cell.
chromosome
chromosomes.
52
a leukemic
progressively.
number
extra
151
ABERRATIONS
in
development
an
higher
it
is
others,
of
change
in genetic
case
particularly
in
aberration
oc-
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
152
KIOSSOGLOU,
curs,4’66’75
association
in
tivity.2’91
In
this
chromosomal
somes,
anomaly,
are
phatase
to
activity.2’91
It
of these
patients
carried
on
G 21
trisomy
or
appears
the
of
pair
of
in
extra
the
in
cells
somes
appeared
errors
from
G
possessed
a possible
we
we
“regular”
type
healthy
trol
in
iso-X
were
of
of
(G
21
chromosome
aneuploidy
and
to
in
B series.
This
the
chromo-
successive
22,
F
All of the
im-
abnormal
autosomal
G
it
cumula-
19-20,
D
abnormal
13,
cells
as well.
examine
an
family
although
multiple.
toward
appear-
mechanism.
were
the
forms
the
known,
with
form
genetic
ring
for
pattern
concerning
the
of
replicating
progression
E, C and
in
loss
polyploidy,
in the
progressing
the
material
is not
error
evolutionary
this
example
syndrome.
the
genes2
variety
mechanism
anomalies
alterations
Down’s
members
lobe
by
G 21
occasionally
The
a repetitive
was
phos-
their
genetic
only
aneuploidy,
an
chromosome
he
the
followed
unable
that
of
Thus,
chromosomal
21
Down’s
is regulated
)
.‘
with
alkaline
polymorphonuclear
which
extra
hand,
represent
involving
feel
of
chromo-
Patients
regardless
and
other
The
an
eventually
Although
the
patient.
D 14 and
leukemia,
present
chromosomal
to show
starting
a translocation
acrocentric
low
control,
occur.5’34’39’45’7#{176}
material
this
ac-
determinants.2,4,4’55’89’90
AGL
may
case,
of
perhaps
smallest
the
translocation
to
this
genetic
hemic
tive
genetic
the
multiple
that
present
balance
that
well-defined
known
or
possible
DAMF.SHEK
phosphatase
polymorphonuclear
chromosomes,
with
On
are
or
the
AND
alkaline
mongolism.37’55
chromosomes34’42’45’97
fragments
ance
in
possible
of
patients
determinants.34’45’76’77
seems
of
elevated
13-15/21
of supernumerary
and
have
is also
several
the
one
is under
reciprocal
to have
Some
PMN
is a deletion
is involved
known
count
low
MITUS
chromosome).
chromosome
syndrome
very
involving
( Ph1
G 21
same
a
there
material
the
The
with
ROSENBAUM,
patient
The
was
before
of trisomy
degree
much
of
higher
the
G 21,
onset
that
in
found
his
the
aneuploidy
than
of
representing
in
three
a
con-
population.17’76’77
The
normal
karyotype
of the
which
otherwise
phenotypically
mongoloid
their
the
children.27
parents
favors
father
The
the
excluded
an F 19 trisomv
syndrome
normal
fathers
may
be responsible
for
absence
sporadic
of a GIG
appearance
or
of
translocation
a DIG
Down’s
syndrome
in
in
this
family.100
It has
been
mother
suggested
is responsible
lar
genetic
the
age
had
anomaly
of
17
of
in
revealed
campi.
An association
and
mental
disjunction
syndromes.
the
twin
been
resulting
sister
of
cerebral
in the
One
the
first
set
The
possibility
atrophy.
consistent
with
a D
of
the
between
cerebrum,
these
of
substantiated
possible
by
reported.61’#{176}#{176}’82
A tendency
in profound
aneuploidy
was
who
trisomy
thalamus
chromosomal
demonstrated
died
that
and/or
at
she
syndrome6#{176}
One
of
by autopsy
to meiotic
of the
a simi-
exists
anomalies,
clinical,
cells
postulate
twins
13-15
cerebellum,
two
germ
may
pattern
such
as E 16-18
trisomy.2’
a D 13-15
trisomy,
is suggested
atrophy
retardation
has
nondisjunction
trisomic
aberrations
anomalous
perhaps
which
findings,
meiotic
the
widespread
chromosomal
or another
syndromes,
that
for
these
two
findings
and
hippo-
D 13-15
trisomy
and
autopsy
mitotic
in the
nonpresent
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
(;HItOMOSOMAL
Similar
family.
possibility
familial
exists
tendency
that
tion
occurs
occasionally
although
he
favoring
a
with
be
the
may
mentioned,
healthiest
mother,
of
older
genetically.
The
same
in whom
been
the
however,
that
For
( M.M.
to the
satellite
tendency
to
nondisjunc-
this
reason,
) and
the
grandmother,
nondisjunction
applies
anomaly,
( N.
older
association
was
The
1
327
influence
tissues.24’6#{176}
daughter
determined
caution.
( R. M. ) brothers,
younger
for
the
has
factors
should
in
in
interpreted
genetic
It
findings
to nondisjunction
some
nondisjunction.14’30’31’71
positive
153
ABERRATIONS
must
)
M.
the
and
a possible
CUSC
nondisjunction.24
Another
intriguing
ning
events
this
appears
family
tion
to be
more
any
the
concomitant
mental
Advanced
other
development
cated
in some
age
as
well
hand,
the
affecting
CIS
felter’s
different
age
of
noxious
agents
acute
leukemia
and
tion.’8’8’#{176}8 X-ray
exposure
netic
factor
several
been
confirmed
by
by
( pelvimetry
posure
type,
which
notably
by
in
various
On
the
the
seems
general
affected
incidence
sex33
seems
to
E series,82
such
as
C 21
tn-
syndromes.
to the
also
and
predispose
C series
retardations
with
aneu-
of
tnisomic
to predispose
of
hand,
between
paternal
age has
such
as G 21 trisomy
D or
attentypes
other
one
relationship
or
in this
drawn
of
and
child;
occurred
have
normal
The
influencing
The
ultimate
been
sex
to
implianoma-
autosomal
chromosomes82
XXXXY62
as
or
Kline-
of the
others.’5’8#{176}
) during
results
in
and
non-specific
in some
In
the
total
the
8th
been
of Down’s
present
case,
to
as
being
of
x-ray
radia-
as a pathoge-
these
findings
there
was
of pregnancy;
radiation
syn-
is ionizing
incriminated
although
month
body
pathogenesis
in childhood
has
McMahon,58
damaging
effects
patients
role
of
with
AGL
in
particularly
xylol,
That
toluol,
some
benzene.
influence
appears
per
in the
that
se,
the
most
but
High
chemicals
established,9’19’29’35’38
stimulating
mother
documented.’2’16’86’8#{176}
etiologic
specific
in the
malignancies
have
one
an exposure
the
fetus,
has
significant
not
x-ray
ex-
of this
been
cited,
statistically
as
a
agent.
adequately
volved
implicated
other
authors,18’84’#{176}2’98
Witts98
leukemogenic
It
not
and
one
factor
mental
of the
drome,
had
twinning
with
Advanced
anomalies
the
had
authors
autosomal69’82
age
types
event
twin-
affected
syndrome.99
One
The
other
same
parental
This
heterokaryotic
somatically
syndrome.33’56’96’9#{176}
is a factor
as
lies.#{176}2’T#{176}
Advanced
one
described.56’06
to be elucidated.
of neoplasia.63’85
nondisjunction
syndromes
of
twins
have
been
remains
double
and
Different
Down’s
trisomy
well
coincidence.
appearance
maternal
somy,’4’23’30’82’85
is the
normal
generation.
of heterokaryotic
syndrome
and twinning
the
than
including
cases
Down’s
ploidy
family
of one
previous
retardation
isolated
of this
a pattern
during
to
On
aspect
with
may
act
as
human
case
lighter
agents
precipitating
a new
clone
chromosomes
exposure
of
of
in this
in
cells
also
well
such
as
per cent kerosene)
case seems
remote.
postnatal
agents
of
is
solvents
(100
in-
leukemia.12”8’#{176}2
leukemia
aromatic
fluid
is
is probably
granulocytic
of leukemia
noxious
of
chronic
the
ingested
the
on
x-ray
development
development
of
development
and
the
in
the
dosage
life
“trigger
possessing
may
not
mechanisms”
neoplastic
be
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
154
KIOSSOGLOU,
characteristics.
A better
acquired
cytogenetics.
genetic
To
our
drome
in
found
understanding
imbalance
knowledge,
of
patient
with
a possible
AGL
and
this
first
Of
and/or
of
of
human
Down’s
syn-
aberrations
particular
) tendency
DAMESHEK
area
case
chromosomal
twinning.
( maternal
AND
of inherited
to solve
the
multiple
MITUS
nature
in order
of
familial
true
exemplifies
a constellation
in association
presence
of the
is necessary
this
which
ROSEN13AUM,
were
interest
was
the
to nondisjunction.
SUMMARY
1. A case
with
of Down’s
twinning
were
found
prior
2. The
to
53,
cell
42
and
3.
The
5.
possible
healthy
6.
)
sets
of
x-ray
trisomic
the
one
(C
21
Multiple
therapia
2.
49
ab
ad
cellulas
(con
3.
53
e ab
leucemic
de
4. Geminage
5.
Un
6.
possibile
Multiple
( 74.2,
been
are
IN
con
series.
affected
was
) and
( normal
demonstrated
in
in iste
be
and
parental
of
enand
three
etiolog’ic
factors,
age
briefly
such
in the
as
im-
ioniz-
development
discussed.
INTERLINGUA
de
Down
(trisomia
geminage
e acute
esseva
modal
80,
agents
neoplasia
syndrome
52
74.2,
tendentia
constant,
D
one
might
variava
chromosomas.
per
G 21)
ante
47
Le
predominante
ad
53,
puero
granulocytic.
e durante
ab
51
in un
leucemia
trovate
le chimo-
subsequentemente
population
chromosomas
in
tres
de
occasiones
e 79.5).
autosomatic-trisomias
vices
49
leukemic
occasions
and
normal
has
and
representate
heterocaryotic
duo
del
signification
ad
predominantemente
incontrate
normal
42
aberrationes
e afficeva
de
numero
esseva
procentages
Le
subsequently
three
F
and
and
injurious
chromosomatic
le
normal
chemicals
associate
aberrationes
antileucemic.
G,
anomalies
process.
different
caso
etate,
Initialmente
and
overwhelming
polysomies-were
the
trisomy
nondisjunction
and/or
un
de
of
nondisjunction
syndromes
4 annos
aberrations
family.
exposure,
describite
1. Es
53
on
and
SIJMMARIO
de
4, associated
twins.
to
mitotic
radiation,
to
51 chromosomes
with
of
in the leukemic
implication
of
The
7.
47
The
chromosomes
family
tendency
Multiple
ing
this
members
portance
of
the
in
affected
A
from
respectively.
twinnng
twice
mentally
ranged
by
age
chromosomal
chemotherapy.
aberrations-trisomies
Heterokaryotic
4.
Multiple
respectively).
predominantly
countered
) in a boy,
trisomy
antileukemic
represented
autosomal
involving
during
chromosomes
cent
21
described.
number
52
was
per
79.5
is
and
modal
to
population
80
AGL
to
initial
and
(G
syndrome
and
e polysomias-esseva
le chromosomas
del
con
normal
un
membro
series
constante
C, F, e D.
e le altere
afficite
esseva
familia.
nondisjunctori
esseva
demonstrate
in
tres
membros
familia.
anormalitates
etiologic
de
in le processo
nondisjunction
leucemic.
mitotic
es
possibilemente
de
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
MULTIPLE
CHROMOSOMAL
Le
7.
sante,
incriminabilitate
exposition
discutite
de
de
a radios
brevemente
trisomia
e/o
155
ABERRATIONS
ab
de
vane
X,
nocive
agentes
substantias
le puncto
de
e factores-radiation
chimic,
etate
del
disveloppamento
vista
del
ioni-
parentes,
etc.-es
de
syndromes
neoplasia.
ACKNOWLEDGMENTS
wish to thank
l)r. Frederick
preparation
of this paper.
We
the
in
W.
Gunz
and
Dr.
Jerome
Lejeilne
for
helpful
advice
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MULTIPLE
CHROMOSOMAL
Kosmas
A.
Blood
Kiossoglou,
Research
Hospital,
159
ABERRATIONS
M.D.,
Research
Laboratory,
and
Assistant
Pratt
in
Medicine,
of Medicine,
Ernest
tology,
II. Rosenbaum,
Blood
Research
land
Center
cine,
Mount
W.
I.
Mitus,
tolo gist,
land
Center
William
tor
land
of
Research
Center
M.D.,
Research
Hospital,
versity
School
now
Associate
School
Dameshek,
Center
University
School
San
and
Chief
Professor
of Medicine,
of
in
Franciso,
of
Boston,
Hematology
Pratt
of
Eng-
Mass.
and
Mass.
Calif.
Medicine,
Clinic-New
Medicine,
Boston,
Medi-
Hema-
Clinic-Netv
Professor
of Medicine,
HemaEng-
Assistant
Pratt
Assistant
Laboratory,
and
Assistant
Center,
Laboratory,
and
University
Blood
hematology,
Mass.
Mass.;
Medical
Research
Hospital,
Tufts
Tufts
Boston,
Boston,
Hospital
M.D.,
Blood
in
England
M.D.,
formerly
Trainee
in
Laboratory,
Pratt
Clinic-New
Hospital,
Zion
Fellow
Clinic-New
DirecEng-
Tufts
Uni-
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
1964 24: 134-159
Multiple Chromosomal Aberrations in a Patient with Acute Granulocytic
Leukemia Associated with Down's Syndrome and Twinning: Study of a
Family with a Possible Tendency to Nondisjunction
KOSMAS A. KIOSSOGLOU, ERNEST H. ROSENBAUM, W. J. MITUS, WILLIAM DAMESHEK and Carol
Sheehan
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