From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
Near-Haploid
Acute
Lymphoblastic
With
By
We
Garrett
describe
two
leukemia
whose
lymphoblasts
acid
Schiff
by
two
which
of
while
and
was
with
the
second
a minority
with
content
an
initially
had
28.
our
markers
with
near-haploid
ALL.
patient
were
adolescents,
and
surface
Each
near-haploid
and
doubling
of
had
the
predominant
and
a few
cells
with
with
analysis
minor
near-
a
of
cytometric
one
of
near-haploid
56
DNA
popula-
review
two
mo).
for
each).
Thus.
and
initial
evaluation
ratory
features
on the
Schiff
associated
with
high risk
potentially
features
a poor
and
laboratory
prognosis
so that
of relapse
can be identified
more
effective
therapy.2
of leukemia
cells
chromosome,
which
usually
signifies
a poor outcome.46
and prognostically
distinct
identified.
leukemia
We
cells
report
were
patients,
as well
with near-haploid
genetically
lar clinical
at
treated
with
cytogenetic
have
been
noted
occurs
in B-cell ALL and
No other
cytogenetically
subgroups
have
yet been
as four
ALL,7”
with
ALL
whose
Analysis
of these
previously
suggest
reported
that this
CASE
percent
esterase
neously
form
induced
and
cal
methotrexate,
therapy
trexate.
She
pallor,
bone
blasts
white
Research
Hospital
migratory
bone
girl
(SICRH)
pain,
hepatosplenomegaly
and
and
and
weight
to
had
a 4-wk
loss.
Physical
submandibular
St.
Jude
history
failed,
and
Jude
the Divisions
Patient
Children’s
Supported
CA-21765.
Research
in part
Hospital,
by
Memphis.
Cancer
Program
Leukemia
and
Center
of
Project
Grant
I
showed
included
Labo-
Pathology,
St.
Grant
and
AISAC.
Submitted
Address
December
reprint
1 7, 1980;
requests
accepted
to Garrett
ofHematology/Oncology,
St. Louis
Kingshighway
St. Louis.
© 1981
Boulevard,
by Grune
& Stratton,
0006-4971/81/5801-0002$01.O0/0
14
Inc.
February
M.
Brodeur,
Children’s
Mo.
63110.
24, 1981.
M.D.,
Hospital.
and
(CNS)
until
prophylaxis,
of intrathe-
the
patient
began
and
weekly
metho-
the
fifth
circulating
month
blasts
when
returned.
to those
at diagnosis
but
not
conventional
did
and
was
vincris-
5 doses
and
identical
from
remission
prednisone,
and
antiserum
.
Bone
total
blasts
react
and
with
experimental
Ia
drugs
diagnosis.
Division
500 South
(L-I
referred
sore
with
formation
of
marker
and
Bone
CSF
marrow
of prednisone,
tion
complicated
L-asparaginase,
prophylaxis
methotrexate
homogeneous
black,
with
was
common
and
normal.
was
achieved
and
patient
rads
(I2
fractions)
administered,
and
and
weekly
were
with
a
negative
for
A
standard
with
chest
4-wk
Since
induc-
to prednisone
and
and
this
of
were
positive
antigens.
secondary
hospitalized
results
stains
L-asparaginase.
was
lympho-
but
ALL
were
vincristine,
1 800
blasts
in
aspirates
The
esterase
of marrow
Ia
presented
ALL;
PAS.
and
by hyperglycemia
the
mercaptopurine
small
immunoglobulins
studies
appreciable
are
of
surface
remission
regimen
without
for
a 2-wk
examination
diagnostic
stained
studies
and
after
Physical
each)
with
which
SJCRH
at diagnosis
were
Sudan
against
radiograph
cm
replacement
95%
peroxidase.
Surface
was
(5
to
throat.
features
studies
marrow
type),
E-rosette
daily
was
and
marrow
negative.
by
girl
fatigue,
Laboratory
heteroantisera
(CORE)
CA-20/80,
Ia
cerebrospinal
marrow
system
and
hepatosplenomegaly
Table
fatigue,
white
pallor,
of
Tenn.
Support
spontasurface
2
I 1-yr-old
lymphadenopathy.
lymphadenopathy.
ofHemaio/ogy-Onco!ogy
not
against
with
treatment
ALL
I I mo
or express
mercaptopurine
with
she died
Children’s
findings
common
did
(E)
and
bone
radiation
morphologically
the
acid
black,
simi-
studies
From
were
periodic
Sudan
blasts
radiograph
administered
this
with
peroxidase,
therapy
daily
on
vacuoliSeventy-one
heteroantisera
made,
splenomegaly,
Reinduction
An
referred
well
pain,
with
antiserum.
REPORTS
was
did
with
marrow
population
cytoplasmic
pattern
nervous
then
content
normal.
was
of cranial
was
maintenance
with
A chest
these
cytoge-
classification”).
with
unique
detect
of DNA
prominent
Marrow
induction
rads
patients
a
I . A bone
erythrocytes
Central
of 2400
(four
ALL.
in Table
in a block
were
daunomycin.
consisting
FAB
of ALL
by a standard
tine,
with
by
negative.
examinations
10
or without
by a heterogeneous
size,
react
five
included
with
antigens.’3
a diagnosis
have
analysis
sheep
X
To
of patients
listed
girls,
represent
we
of studies
did
or
to
(median,
with
prognosis.
are
with
but
(CSF)
After
revealed
17-yr-old
were
ALL”
reacted
1
A
stains
rosettes
18,
by
reported
were
21
cytometric
stained
results
immunoglobulin
“common
history
Patient
blasts
The
five
may
replacement
of normal
of the
and
flow
morphology
(PAS).
14,
ALL
a poor
marrow
(L-2
The
patients
is a cyto-
subgroup
of ALL
with
and a poor prognosis.
zation
10.
been
survivals
chromosome
at diagnosis
showed
fluid
the Philadelphia
chroa distinct
subgroup
of
and the 14q+
marker
two patients
near-haploid.
recognizable
characteristics
patients
and
Two
at diagnosis
to have prognostic
significance:
mosome
(Ph’ ), which
represents
ALL
with a poor prognosis,3
features
aspirate
six,
later
In addition
have
short
subgroups.
analysis
confirmed
sample.
these
had
for
with
in our
of lymphoblasts
of clinical
ALL
possible
ESPITE
considerable
progress
in treatment
of
childhood
acute
lymphoblastic
leukemia
(ALL),
30%-50%
of patients
still do not survive
more than 5
yr from diagnosis.’2
Recent
emphasis
has been placed
Of
five
Kalwinsky
was
patients
near-haploid
of
other
netic
four
disomy
K.
marrow
chromosomes
subgroup
David
which
the
only
six had
disomy
and
of
patients,
All
and
patient,
periodic
D
identification
second
with
chromosomes
the
in the
Bowman,
cytogenetic
patient
Flow
Paul
near-haploid.
a predominance
detected
tion
W.
lymphoblastic
exact
26
Look,
were
one
first
Thomas
acute
pattern
Subgroup
Prognosis?
cells
ALL”
blasts.
A.
A Unique
with
“common
The
cells
L. Williams,
in a block
of
karyotype.
population
girls
a Poor
immunofluorescence.
populations
haploid
52.
had
indirect
hyperdiploid.
Dorothy
leukemia
stained
and
confirmed
Brodeur,
adolescent
(ALL)
Their
had
M.
Leukemia:
given
5 doses
patient
methotrexate
insulin.
and
CNS
of intrathecal
is now
at
receiving
month
6
of
remission.
Blood,
Vol. 58,
No.
1 (July),
1981
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
NEAR-HAPLOID
15
ALL
Table
1 . Clinical
Age
Reference
WBC
at Diagnosis
Findings
Platelets
for Six Patients
13.5
155,000
98
Pos
10.7
22,000
99
Pos
100
Pos
ND
0
5
Pos
ND
7
10
ND
Common
Neg
Non-T.non-Bt
1
17
F
34.000
11
F
3.500
7
14
M
57.700
7.4
12,000
8
5
F
120.000
5.9
15.000
91
9
12
F
87.000
8.5
50.000
100
11
17
F
13,800
6.7
37.000
96
evidence
of spontaneous
rosette
MATERIALS
Cytogenelic
Bone
from
marrow
diagnosis.
to a modification
trypsin-Giemsa
of
sheep
erythrocytes
METHODS
cytogenetic
and
were
prepared
of the
technique
bone
into
agulant.
was
analysis
relapse.
and
were
from
for cytogenetic
of Tjio
used
A
small
obtained
patient
analysis
and
2 at
according
Whang.’4
for chromosome
sodium
citrate
capillary
A modified
banding.’
directly
to
for
within
samples
I 0 mm
stained
standard
The
relative
iodide
cells
nm),
and
a system
relative
form
ofa
frequency
General
histogram
with
the
of filters
fluorescence
to a Data
Survival
mo)
(mo)
Common
5
11
Common
6 +
fluorescence
at a rate
Eclipse
cell
These
of
of 50-100,000
normal
cells
blood
G0/G1-phase
each
TPS-l
In this
instrument,
single
beam
excitation
of the
propid-
was
quantitated
after
passing
Measurements
were
were
7 +
6
9
16
31
plotted
units
ofthe
cell,
divided
measured
derived
relapse,
mated.
differed
or
46
detected
by indirect
chromosomes
with
random
immunofluorescence.
appeared
to be
chromosome
loss
normal
that
were
from
normal
cells.
At both
diagnosis
and
an identical
clone of 26 chromosomes
predomThe stem-line
karyotype
with 26 chromosomes
from a haploid
karyotype
(one each of chro-
mosomes
1 to 22 and X) in that chromosomes
14, 21,
and X were
in two copies.
The metaphase
with
52
chromosomes
could
not be completely
analyzed,
but
probably
represented
a doubling
of the 26-chromo-
karyotype.
type
is shown
A representative
in Fig.
metaphases
near-haploid
karyo-
I.
from
the
bone
marrow
of patient
2 were
analyzed
at diagnosis;
4 contained
46 chromosomes
and 36 contained
55-56
chromosomes
with the
modal
number
56. However,
4 additional
metaphases
with
28 chromosomes
were
found
after
the results
from flow cytometric
analysis
of DNA
content
were
known.
The metaphases
with 28 chromosomes
had a
karyotype
plus
5 extra
chromosomes:
+
+E,
+G,
identified
by banding
as chromosomes
14, 18, 21, and
X. The
metaphases
with
chromosomes
were
haploid
karyotype.
an
exact
doubling
of
the
2C,
56
near-
of
recorded
transferred
and
44
or cells
+D,
10,
sorter
laser
with
haploid
propid-
cell
argon-ion
G0/G1-phase
was
with
laser
data
showed
of
analyzed
as a reference
stained
of all cells
computer.
that
intensity
The
allowed
normal
use
photomultipliers.’7
histogram.
intensity
content
and
were
immunoglobulin
cells
Forty
fresh
solution.
model
Fla.).
intensities
an abscissa
fluorescence
of cells
the
in each
of
at 4#{176}C
and
to a focused
from
complex
jl
of normal
a Coulter
exposed
cells/mI.”
50
of stained
for
0.1%
cells.
Hialeah,
fluorescence
iodide-DNA
through
by
were
stored
mixed
intensities
Inc.,
in suspension
106 white
iodide
fluorescence
leukemia
analyzed
Electronics,
(488
PAS
or of surface
some
added
and
solution
numbers
were
modal
of the
fluorescence
were
(Coulter
then
was
adding
iodide
were
cells
the
of
by
were
antico-
mg/mI)
I ml of propidium
leukemia
to that
(0.05
dilution
equal
crest
citrate
suspension
iodide
in propidium
at 4#{176}C,
and
to identify
relative
iliac
sodium
marrow
prepared
24 hr. Approximately
and
posterior
3.8%
this
a final
were
blood
to stain
of
samples
or marrow
the
contained
of propidium
to achieve
blood
from
that
volume
to a solution
Normal
marrow
a syringe
directly
DNA
with
Cytonietry
Samples
the
for
diagnosis
technique
aspirated
ium
AND
samples
I at
Samples
Flow
formation
Studies
patient
ium
Surface
Markers
determined.
tNo
cells
complete
Remission
(cells/MI)
2
cells
ALL
Sex
Our patient
blood
Near-Haploid
(yr)
(cells/il)
Marrow
1% Blasts)
With
Hb
(gIdl)
Ourpatient
‘Not
or
and Laboratory
in the
directly
as a frequency
DNA
by
blood
for each
index
the
(Dl,
modal
cells).
The
histogram,
of 500 cells/sec.
RESULTS
(.)‘logenelic
Banded
Findings
chromosomes
of the
leukemia
cells
from
the
bone marrow
of patient
I were analyzed
at diagnosis
and
at relapse.
Of
the
original
28 metaphases
analyzed,
24 metaphases
contained
26 chromosomes,
2 had 25 chromosomes,
I had 44 chromosomes,
and I
had 52 chromosomes.
At relapse,
27 metaphases
were
analyzed.
Twenty-six
metaphases
had
26 chromosomes
and
I had 46 chromosomes.
The metaphases
Fig. 1 .
Karyotype
of the lymphoblasts
from patient
1 . The
karyotype
consists
of 26 chromosomes:
a haploid
set (one copy
each of chromosomes
1 to 22 and X) with
an extra
copy of
chromosomes
14. 21. and X.
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
16
BRODEUR
l0000
ET
AL.
I
1-Leukem,o-
i
G0/G1
(near-haploid)
9,0008,000
-
7000
-
U)
ci)
(__)
U,
0
,-
5,000-
a)
I
z
3 000
Normal
2 000
.
I ,000
-
Leukemia
)
i
0
.2
.4
G2/M
-
( near
-
0-
haploid)
-
I
I
I
1
I
.6
.8
.0
.2
.4
.6
Index
(DI)
DNA
Flow
I
and
represented
predominant
malignant
0,000
I
2.2
only
I
2.4
2.6
26 chromosomes.
A smaller
peak
of cells
in
this histogram
had a DI of 1 .0 and thus represented
a
small
proportion
of normal
marrow
cells
in G0/G,
phase.
There
was no evidence
of a peak of cells with a
DI of 1.16, which
would
have indicated
that another
patient
I is shown
in Fig. 2. The
peak of leukemia
cells had a DI of
the
I
2.0
with
Cytometry
lymphoblasts
from
main G0/G,-phase
I
I
.8
DNA
histograms
of the leukemia
cells from
both
patients
were analyzed
at relapse
(patient
1 ) or diagnosis (patient
2). The DNA
histogram
of bone marrow
0.58
Fig. 2.
The DNA histogram
of
marrow
lymphoblasts
from
patient
1 at relapse
shows
a peak
with
a modal
Dl of 0.58,
corresponding
to the G,/G,-phase
loukemia cells with a karyotype
of 26
chromosomes.
Leukemia
cells in
the DNA synthesis
phase
of the
cell cycle have increasing
levels of
DNA
and
are
evident
at
Dl >0.58.
The small peak of cells
with a Dl mode of 1 .0 represents
residual
normal
G,,/G,-phase
cells
in the marrow.
Leukemia-S
clone of leukemia
cells
tion of the near-haploid
clone
had resulted
karyotype.
from
the
duplica-
-
-Leukemia
-
9,000
G0/G1
-
( hyperdiploid)
8,0007,000U)
a)
)U,
C
-
0
Fig. 3.
The bone marrow
DNA
histogram
of lymphoblasts
from
patient
2 at diagnosis
shows
a
small peak with a Dl mode of 0.59.
This peak represents
the G.,,/G,phase
cells
of the
near-haploid
leukemia
clone
with
28 chromosomes
per cell. The large peak of
cells with a Dl mode of 1 .1 9 reprosents G,, /G1 -phase
cells from the
hyperdiploid
leukemia
clone
that
resulted
from doubling
of the nearhaploid
karyotype.
The
skewed
region
of this
peak
(Dl of 1.0)
corresponds
to residual
normal
cells
in this
leukemic
marrow
sample.
‘.-
ci
I
5,000-
4,000-
Normol-G0
3,000-
Leukemia(near-
/G,
G0/G1
haploid)
2,0001,000C’I
I
0
.2
I
I
.4
.6
I
.8
I
.0
DNIA
I
.2
I
I
I
1.4
1.6
1.8
Index
(DI)
I
2.0
I
2.2
I
2.4
I
2.6
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
NEAR-HAPLOID
ALL
The
DNA
lymphoblasts
complex
histogram
of patient
(Fig.
3).
with
a Dl of0.59
the
near-haploid
number
17
from
2 at
In this
histogram,
represented
By
in the
the
small
cells
integrating
histogram,
the
we
found
established
as a cell line.’0 This
ity may not be peculiar
to ALL,
peak
the G0/G,-phase
clone.
of cells
the
bone
marrow
diagnosis
was
more
three
of
cases
this
population
of near-haploid
cells represented
4% of the
total marrow
cell population.
The major
peak on the
histogram
with a DI of I . I 9 represented
the predomi-
three retained
the
9 and 22.
It is not known
nant hyperdiploid
clone,
which
of the near-haploid
clone.
The
Dl
1.0 was due to normal
precedes
However,
was an exact
doubling
left skew of this peak at
G0/G,-phase
cells that
=
represented
3% of the total
marrow
cell
extremely
ALL
have
rare.4
been
is noted
near-haploidy
Only
previously
four
in
only
l%-3%
appears
to
cases
reported.7t’
of
of
be
near-haploid
The clinical,
laboratory,
and
cytogenetic
features
of our
two
patients
are strikingly
similar
to the four
patients
reported
so far (Tables
1, 2). Five of the six patients
were girls and five were adolescents
(median
age I 3
yr, range
5-17
yr).
typical
lymphoblasts,
and
had
a coarse
blasts
patients
common
tested
had
ALL surface
The
with
dom
Morphologically,
usually
with
chromatin
that
were
stem
line
a mode
pattern
their
scant
non-T,
marker
in the
six
non-B
pattern
(I patient)
(3 patients).
patients
was
haploid
karyotype
all six had disomy
for chromosome
disomy
for chromosome
10, 14,
each,
see Table
be responsible
by Oshimura
proposed,
the
It
is
for
et
most
of chromosomes
2). The
remarkable
that
2.
cells
of
a
1 to 22
that
with
a
survival
cells from
Cytogenetic
and
one
Features
Reference
1
+ 2 1
+10,
+14.
26,XV,
+0(14),
27,XX,
+10,
9
27,X,+1O,+14,+18,+21
11
Karyotype
+ 1 4,
28,XX,
is expressed
relative
tIn each case, the hyperdiploid
+6,
to a haploid
mode
to hyperdiploidy
is a common
finding
it is possible
that
is currently
recognized.
clones
clones
However,
presence
the
The
on cytogenetic
analysis
or the
by flow cytometric
analysis
of
of
at Diagnosis
+21
in acute
leukemia
cells
for
a large
coworkers
for Six Pat ients
chromosomes):
of the
one
each
near-haploid
Near-Ha
Diploid
4
9
+21
With
Percent
98
doubling
the
espe-
by
content
92
(23
for
be
for
the most definiof near-haploid
were
These
authors
found that DNA
a sensitive
and reliable
means
an exact
near-
lines
could
preparations
and
+18,
some-
from
nearALL may be
expression
of polymorphism
or
of even numbers
of all chromosomes,
chromosomes.
would
be
be
at the time
it may
early
clonal
evolution
and that near-haploid
than
may
early.
Barlogie
Cells
of the
DNA
+21
karyotype
represented
a doubling
patients.2’
etry was
Marrow
Regardthe near-
DNA content,
as in our second
patient.
The advantages
of flow cytometry
for the analysis
+G(21)
+10,
with
near-haploid
+18,
+18,
result
in loss
and differen-
transformation.
that establish
origin
of hyperdiploid
stem
by close inspection
of banded
Near-Haploid
28,XX,
7
frequent
the
lines
Percent
26. XX.
transformation
near-haploid
state.
would
permit
the
proliferation.
patient
were
of Bone
8
reflect
stem
and hyperdiploid
detection
of both
might
lymphoid
chromosomes
malignant
subclones
of ALL,
cially marker
tive evidence
Karyotype’
Ourpatient2
line,
hyperdiploidy
homologous
presence
Near-Haploid
Our patient
whether
from near-haploidy
frequent
but also
haploid
detected
2 1 , with or
18, or X (4
mechanisms
transition
not only
more
near-haploidy
have been discussed
al.9 Of the
several
mechanisms
feasible
is multipolar
mitosis.
karyotype
are capable
Indeed
the near-haploid
Table
each
stem
times
haploid
near-haploid
and X),
without
cases
(one
between
of recessive
genes that might
control
of lymphoid
growth
of diagnosis
or
of 26-28
chromosomes
and had a nonranof abnormalities.
In addition
to having
in
myelogenous
of these
cases
except
that
all
near-haploid
karyotype
may frequently
result.
Five of
the six patients
had a second,
hyperdiploid
population
(52-56
chromosomes)
with an exact
doubling
of the
near-haploid
karyotype
at some
time
during
the
disease
course.
That
the hyperdiploid
clone
predominated
at diagnosis
in two patients
suggests
that
the
Since
cells were
cytoplasm
pattern.
At least four patients
PAS
positive,
and
the
four
a
translocation
tiation,
leading
to malignant
less of the sequence
of events
haploid
hypodiploidy
with
ALL,
abnormalare at least
near-haploidy
or results
from
the
a near-haploid
genome
expression
of regulatory
population.
DISCUSSION
Since
patients
of
blast
crisis
of Ph’-positive
chronic
leukemia
in adults.’82#{176} The karyotypes
were
similar
to those
reported
here,
total
that
additional
cytogenetic
since there
ploid
reported
series
of
ALL
Percent
Hyperdip$oid
4
9
82
2
0
58
42
0
21
0
79
70
10
20
of chromosomes
mode.
1 to 22 and X.
adult
flow cytomof detecting
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
18
BRODEUR
clones
with
number
abnormal
of
(<45
DNA
or >52
was
chromosomes).
cytometry
could
content
content,
chromosomes
provided
They
measure
that
sufficiently
also
noted
that
abnormalities
in G0/G,-phase
cells,
the
abnormal
flow
of
independent
DNA
of prolifer-
ation
that is required
for karyotyping.
Further,
there
was
surprising
agreement
between
the number
of
extra chromosomes
in the leukemia
cell karyotype
and
the increase
in DNA
content
measured
by flow cytometry.
Improved
detection
of
near-haploid
ALL
important
to clinical
as well as biologic
this subgroup
appears
to be associated
prognosis.
Unlike
the poor
ALL,
which
occurs
more
may
studies,
with
prognostic
frequently
be
since
a poor
group
of T-cell
in older
boys,2
near-haploid
ALL
is associated
with
the common
ALL
phenotype
and appears
to be more
frequent
in
adolescent
girls.
For the five patients
with adequate
follow-up,
the
and
the
durations
median
remission
median
survival
are considerably
duration
was
was
10 mo. Both
shorter
than those
for children
with ALL treated
with modern
In addition,
four of the six patients
had
count
of >30,000/z1.
predisposes
to
increased
near-haploidy
be
It is possible
a high
white
that
proliferative
6 mo
median
reported
therapy.’
a white cell
consistently
and
an
respond
may
have
extended
Near-haploid
biologically
her
ALL
for
the
early
relapses
that
typify
to conventional
be considered-e.g.,
marrow
transplanta-
remission.
appears
subgroup
unique
to be a clinically
of ALL,
detectable
and
by
karyotype
analysis,
similar
to the subgroup
of Ph’positive
ALL.
Near-haploid
ALL also can be detected
by
flow
cytometry,
even
when
the
duplicated,
hyperdiploid
subclone
is predominant.
Flow cytometry
is a more
sensitive
means
of detecting
small
populations of aneuploid
cells,
necessary
to determine
and
the
chromosome
analysis
specific
numerical
is
and
structural
rearrangements
resulting
in aneuploidy.
These
two laboratory
methods
are complementary
and
should
give important
information
concerning
the biology of
subgroups
near-haploid
of acute
both
patients
ALL
leukemia.
and
For
other
recognizable
these reasons
we are
the
initial
for surface
marker
methods
with
in
evaluation
of
ALL.
count.
It is not known
yet whether
or increased
white count
(or both) could
responsible
poorly
might
or bone
tion, as is being done for other subgroups
of ALL with
a poor
prognosis.
In one patient
with
the longest
survival,
the reappearance
of a near-haploid
cell was
noted
in a hematologically
normal
marrow
after
a
3-mo remission.”
The change
in therapy
at that time
including
near-haploidy
capacity
patients
therapy,
alternate
therapy
more intensive
treatment
ET AL.
ACKNOWLEDGMENT
this
We
subgroup.
It will be necessary
to identify
and follow
additional
patients
to confirm
the predominant
clinical
and biologic
features
of near-haploid
ALL.
If such
thank
Dr.
Seifert
for
editorial
Susan
assistance
Harris,
of
Wanda
Melvin
review.
We
Barry
Somerville,
Lemonds,
and
acknowledge
analysis
the
and
expert
Susan
Hilliard.
Kenna
Williams.
lane
technical
Ann
Tipler,
Ann
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1981 58: 14-19
Near-haploid acute lymphoblastic leukemia: a unique subgroup with a poor
prognosis?
GM Brodeur, DL Williams, AT Look, WP Bowman and DK Kalwinsky
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