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Lack of CD45 Antigen on Blast Cells in Childhood Acute Lymphoblastic
Leukemia Is Associated With Chromosomal Hyperdiploidy and Other Favorable
Prognostic Features
By Fred G. Behm, Susana C. Raimondi, Michael J. Schell, A. Thomas Look, Gaston K. Rivera, and Ching-Hon Pui
The leukocyte common antigen (CD45) was detected on the
surface of leukemic cells in 217 (87%) of 249 cases of newly
diagnosed childhood acute lymphoblastic leukemia (ALL). All
55 cases of T-lineage ALL, compared with 159 of 191 B-lineage cases, expressed the CD45 antigen (P = .0005). The
frequency of CD45 expression did not differ between cases of
early pre-B (CD19+, cytoplasmic p - ) and pre-B (CD19+,cytoplasmic p + )ALL. Cases of ALL lacking CD45 had significantly
lower leukocyte counts (P = .002) and serum lactic dehydrogenase (LDH) levels (P = .007) and were more likely to have
leukemic cell hyperdiploidy greater than 50 (P < .0001) or a
DNA index greater than 1.15 (P < .OOOl), as compared with
cases positive for the antigen. Of the 130 patients whose
follow-up duration was sufficient for analysis of event-free
survival, the 53 with the highest levels of CD45 expression
(290%) were the most likely to have an adverse event on
intensive multiagent chemotherapy. Patientswithout detectable CD45 had a negligible risk of failure. This study suggests
a relationship between the expression of the CD45 antigen
on leukemic lymphoblasts and other biologic factors that
influence prognosis in ALL.
o 1992by The American Society of Hematology.
T
Morphologic and cytochemical studies. Bone marrow cells were
stained by standard techniques, including Wright-Giemsa, myeloperoxidase, Sudan black B, naphthol AS-D chloroacetate esterase,
and a-naphthyl butyrate esterase. The diagnosis of ALL was based
on morphologic and cytochemical criteria of the French-American, * ~ by definition,
British (FAB)Cooperative Working G r o ~ p . ' ~Thus,
all cases had fewer than 3% myeloperoxidase-positiveblasts.
Immunophenotyping. Bone marrow cells were separated on a
Ficoll-sodium metrizoate gradient, and only samples containing
greater than 85% blasts were assayed. Cell surface antigens were
detected by a standard indirect immunofluorescence method using
a panel of monoclonal antibodies that reacted with CD1 (Leu-6),
CD2 (Tll), CD3 (Leu-4), CD4 (Leu-3a), CD5 (Leu-1), CD7
(Leu-9), CD8 (Leu-2a), CDlO (J5), CD13 (MY7), CD14 (MY4 and
Leu-M3), CD15 (MYl), CD19 (Leu-12), CD20 (Leu-16), CD21
(anti-CR2), CD22 (Leu-14), CD33 (MY9), CD34 (HPCA-11
Mylo), CD36 (5F1), CD41 (a-gpIIb/IIIa), CD45 (HLe-l/2Dl),
CD71 (antitransferrin receptor), and anti-HLA-DR. In all experiments, isotype-matched murine myeloma immunoglobulins and
anti-&-microglobulin were used as negative and positive controls,
at the same protein concentrations as the test antibodies. Leukemic cells were also tested for surface and cytoplasmic immunoglobulins (sIgp and cIgp) with goat anti-human p (Southern Biotechnology, Birmingham, AL). An indirect immunofluorescent
technique was used to detect nuclear terminal deoxynucleotidyl
transferase (Tdt).
Fluorescence activity was analyzed by an EPICS C flow cytometer equipped with a 5-W Coherent laser (Coulter, Hialeah, FL) for
HE LEUKOCYTE common antigen, or CD45, is found
on all hematopoietic cells except erythrocytes and
platelets, and is absent from nonhematopoietic tissues.'-'
CD45 antigens belong to a family of cell surface glycoproteins with a heavily glycosylated extracellular domain, a
transmembrane segment, and a large cytoplasmic domain
that contains tyrosine phosphatase
These glycoproteins are encoded by a single gene located in a syntenic
region of chromosome lq32 in humans? CD45 appears in at
least four discrete isoforms that differ in carbohydrate and
protein backbone ~tructure.6.~
Data published by the Third
and Fourth International Workshops on Human Leukocyte
Differentiation Antigens and by others demonstrate that
anti-CD45 antibodies belong to two major clusters groups:
those that detect a framework structure common to all
members of the family, and restricted groups (CD45RA,
CD45RB, and CD45RO) that recognize discrete epitopes
within the variable N terminus of the exterior portion of the
mo1ecule.8.'o-'2Recent findings suggest that CD45 may be
involved in regulation of hematopoietic cell growth, differentiation, and cell
Despite extensive study of CD45 glycoproteins, the
frequency of their expression and potential clinical significance in leukemia and lymphoma remain poorly defined. By
analyzing a large number of consecutive cases of newly
diagnosed acute lymphoblastic leukemia (ALL), we found
that CD45 positivity is related to adverse prognostic features, both clinical and biologic. Patients with undetectable
CD45 expression on their leukemic blasts had the most
favorable presentation and the highest probability of continuous event-free survival.
MATERIALS AND METHODS
Patients. From November 1986 to September 1990,258 consecutive children with newly diagnosed ALLwere admitted to St. Jude
Children's Research Hospital and enrolled in one of two total
therapy studies (XI and XII). Complete immunophenotyping and
cytogenetic analyses were performed on leukemic blast cells from
249 of these patients. Follow-up times were adequate for prognostic determinations only in study XI (n = 130), which tested the
efficacy of six-drug inductionlconsolidation therapy and continuation treatment with rapidly rotated drug pairs." Informed consent
was obtained from all patients or their guardians, and the investigations were approved by the institution's clinical trials review
committee.
Blood, Vol79, No 4 (February 15), 1992: pp 1011-1016
From the Departments of Pathology and Laboratory Medicine,
Hematology-Oncology, and Biostatisticsllnformation Systems, St.
Jude Children's Research Hospital, and the Departments of Pathology
and Pediatrics, University of Tennessee, Memphis College of Medicine,
Memphis, TN.
Submitted January 28, 1991; accepted October 4, 1991.
Supported in part by Grants No. CA-20180 and CA-21765from the
National Cancer Institute and by the American Lebanese Syrian
Associated Charities (ALSAC).
Address reprint requests to Fred G. Behm, MD, Department of
Pathology and Laboratory Medicine, St. Jude ChildrenS Research
Hospital, PO Box 318, 332 N Lauderdale, Memphis, TN381OI.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C.section I734 solely to
indicate this fact.
0 1992 by The American Society of Hematology.
0006-49711921 7904-0017$3.00/0
1011
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1012
BEHM ET AL
monoclonal antibody studies or a Zeiss epifluorescent microscope
for cIgp,, sIgp, and Tdt analyses. Histograms of fluorescent
intensity were based on a log scale. The percentage of positive cells
was obtained by counting the number of events with fluorescent
intensity greater than the isotype-matched negative control.
Leukemic samples were considered positive for a particular
antigen if greater than or equal to 20% of leukemic cells reacted
with a particular monoclonal antibody or if greater than or equal to
10% were positive for CD34, cIgp, and Tdt. The results of CD45
assays in B-lineage ALL were corrected for contaminating normal
T cells in the test sample using the formula [(%CD45 - %CD3)/
(100 - %CD3) x 1001. Because all samples of T-lineage ALL
contained greater than 90% blasts, no correction for contaminating
normal hematopoietic cells was made. Immunophenotyping data
were used to classify cases as T cell (CD7' plus CD5+ or CD2+), B
cell (sIgp'), pre-B (cIgp'), or early pre-B (CD19+, CD22*,
HLA-DR', CD7-, CD5-, cIgp-, sIgp,-, and CDlO').
Cytogenetic and DNA flow cytometric studies. Immediately after
collection, bone marrow specimens were processed for chromosomal analysis by the direct method of Williams et al?l Metaphase
preparations were G-banded with trypsin and Wright's stain.
Chromosome abnormalities were classified according to the International System for Human Cytogenetic Nomenclature.22A sample
was considered to be hyperdiploid if two or more metaphases had a
modal chromosome number of 51 or more. Leukemic marrow
samples were also stained with propidium iodide and analyzed for
cellular DNA content by flow cytometry as previously de~cribed.2~
The results were expressed as the DNA index (ratio of DNA
content in leukemic G,/G, cells v normal diploid G,/G, cells), a
measure that correlates closely with chromosome number. Thus,
the DNA index of diploid cells is 1.00 and that of cells with more
than 53 chromosomes is greater than 1.15.
Statistical analysis. Differences in the distribution of clinical
and biological features among groups of patients were tested by the
two-tailed Fisher's exact test for two-by-two tables or the Pearson
x2 test. The Wilcoxon rank-sum test was used to compare the
percentage of CD45 expression on leukemic blasts of T-cell and
B-lineage cases. The correlation between the percentage of CD45'
blasts and that of other markers was examined using Spearman's
rank correlation. Plots were made using the monotone smoothing
algorithm with a running mean smoother.24 Event-free survival
curves were constructed by the Kaplan-Meier procedure,2' with
differences analyzed by the log-rank and trend tests. Early death or
failure to enter remission was considered an event at zero time.
The effects of potentially independent prognostic factors (age, sex,
race, leukocyte count, serum lactic dehydrogenase [LDH], CD45
expression, DNA index, leukemic cell ploidy) on event-free survival was tested by the Cox proportional hazards model. A stepwise
selection procedure was used to determine factors that were
significantly related to event-free survival. Analysis of treatment
outcome was limited to 130 consecutive patients who were treated
in study XI, as the duration of follow-up for patients in study XI1
remains relatively short.
RESULTS
CD45 expression was detected in 217 (87%) of the 249
cases of childhood ALL. All 55 T-cell cases, compared with
159 of the 191 cases of B-lineage ALL, expressed CD45
(P= .0005). Indeed, expression of the antigen was more
extensive for T-cell ALL than for B-lineage ALL (P= .0003,
Fig 1). The pattern of CD45 expression did not differ
between cases of early pre-B and pre-B ALL. No correlations were identified between levels of expression of CD45
and CD10, CD19, CD21, CD22, CD13, CD14, CD33,
100
n
90
m.
a
m.k.
80
.:
-k
W
70
:
.I
60
50
40
30
20
10
0
B-Lineage ALL
(n = 191)
T-Lineage ALL
(n = 55)
Fig 1. Frequency distribution of levels of leukemic cell CD45
expression among patientswith T- or B-lineage ALL.
CD71, or Tdt. However, CD45 expression was inversely
related to that of the CD20 antigen (r = -.21, P = .002)
and the CD34 antigen (r = -.15,P= .04).
Table 1 summarizes selected presenting clinical and
Table 1. Presenting Features Associated With CD45 Expression in
Children With ALL
% CD45+ Blasts
WBC count (X 109/L)
< 10
10-24.9
> 25
Serum LDH (U/L)
< 300
300-999
z 1,000
Chromosome ploidy
~50chromosomes
>50chromosomes
DNA index
51.15
>1.15
lmmunophenotype
Early pre-B
Pre-B
BS
T
P
22Ot
.06
73
45
99
.002
29
89
33
.05
35
106
67
.007
8
24
116
38
<.0001
171
40
<.0001
14
18
128
30
<.0001
186
30
<.0001
20
12
0
0
105
52
2
0
.68
105
52
2
55
.0005
<20
520.
21
5
6
68
38
53
12
15
4
Values are the number of cases in each group.
*Comparison of B-lineage cases only.
tcomparison of all cases.
SNon-L3, Tdt+ ALL.
P
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CD45 EXPRESSION IN ALL
1013
Table 2. Cytogenetic Findings in the 32 Cases With Low or Absent CD45 Antigen Expression
Case
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Karyotype
48,XX,+X,+4,1S,+der(lg)t( 1;19)(q23;pl3)
Modal number: 59
56,XX,+X,+4,+5,+6,+
lo,+ 14,+21,+21,+i( 17q),+marl/56,XX,+X,+4.+5,+6,+ lo,+ 14,+21,+21 ,+i(17q),+mar2/
55,XX,+X,+4.+5,+6,+10,+14,+21,+21,+i(17q)
55,XX,+4,+5,+6,+
lo,+ 14,+ 17,+ 18,+21,+21/56,idem,+ 11
53,XX,-2,+4,+6,+10,+17,+18,+21,+dup(13)(q?14
+ q22),+mar/53,XX ,-2,+4,+6,+8,+10,+17,+18,+21,dup(13),+mar/
53,XX,+4,+6,-7,+10,+14,+17,+18,+21
,+d~p(13),d~p(l)(q22
+ q42)
55,XY,+X,+4,+6,+ lo,+ 14,+ 17,+ 18,+21,+21 ,i(7q)/55,XY,+X,+4,+6,+ lo,+ 14 ,+ 17,+ 18,+21,+21 ,dup( 1)(q21--* q32)
46,XX,de1(14)(q22q31)/46,XX,i(9q),i(l7q)
54,XY,+X,+6,+8,-9,+10,+14,-15,+17,+18,+21,+21,+dic(9;15)(pll;pll)
,-9,+der(9)t(9:?)(pZ3;?)
55,XX,t(4;8)(p14;p21)c,+X,+4,+6,+8,+10,+ 14,+17,+ 18,+21
60,XY,+X,+4,+5,+6,+8,-9,+?10,+14,+15,+16,+17,+18,+20,+21,+22,+mar
46,XY,t(8: 14)(qll;q32),t(9;22)(q34;ql l),15,+der(15)t(15;?)(pll;?) /46,XY,t(8; 14),t(9;22)i(l7q)/46,XY,t(8; 14),t(9;22)/
51,XY,+5,+ 17,+18,t(9;22),+der(9)t(9;22),+der(22)t(9;22)
54,XY,+X,+4,+8,+14,+
17,+18,+21,+?22
54,XX. +X, +4, 6,+ 14, 17, 18,+2 1, 2 1
55,XY,+X,+4,+6,+
14,+ 17,+ 18,+21,+21,+22
65,XY,+X,+3,+4,+5,+6,+8,+9,+10,+10,+11,+12,+14,+15,+16,+17,+18,+21,
+21,+?19
Modal no.: 53
55,XY. +X, +4, +9, + 10, 14, + 17,+ 18, + 21, + 21
61,XY, +X, +Y, +4, +5, +6, +7, +8,+ 10, 13, + 14,+ 17, + 18, +21, + 21, +22
57,XX,+X,+4,+6,+8,+10,+14,+17,+18,+21,+21,+21,inv
dup(l)(q32 + q12)
52,XY,+X,+4,+6,+
14,+20,+21,i(l7q)/52,XY,+X,+4,+6,+21,+21,i(17q),+mar
46,XY
45,XY,-22,de1(6)(p23),de1(9)(p22),-9,+der(9)t(9;?)(p24;?),- 14,+der(14)t(14;?)(q32;?),t(l;4)(q42;q22)
46,XY,t(9; 13)(p22;q?22)
46,XX
67,XX,+X, +?X,+2, 3, +4, +5, +6, +8, +8, +9, + 10, 11,+ 12,+ 14, + 17, + 18, + 20,+20,+ 21, +21, + 22, - 2, +der(2)t(2;?9)(q33;q?13)
54,XY,+X,+4,+6,+7,+9,+21,+21,+der(?19)t(?19;?)(p13;?)
56,XX,+X,+4,+4,+6,+7,+8,+9,+10,+14.+21,i(17q)
53,XX,+X,+6,+ lo,+ 14,+ 17,+ 18, +21 ,?inv(l 1)(q22q24)/46,XX,?inv(ll I(q22q24)
59,XY,+X,+4,+5,+6,+C,+10,+11,+14,+15,+17,+18,+19,+21
56,XY,+X,+4,+6,+8,+10,+
14,+ 17,+ 18,+21,+21
60,XY,+X,+Y,+4,+8,+9,+10,+10,+14,+18,+20,+21,+21,del(3)(p25),+der(17
)t(17;?)(q25;?)/
6O,XY,+X,+Y,+4,+8,+9,+9,+10,+
lo,+ 14,+18,+20,+21,+21,de1(3)(p25),+marl
56,XX,+4,+6,+ lo,+ 14,+ 17,+ 18,+21,+2l,+marl ,+mar2/56,XX,+X,+4,+6,+ 10 ,+ 14,+ 17,+ 18,+21,+21 ,+marl
+
+ +
+
+
+
+
+
laboratory features of the patients according to the presence or absence of CD45 expression. Cases lacking the
antigen had significantly lower leukocyte counts and serum
LDH levels. Notably, blasts of CD45- patients were more
likely to have leukemic cell hyperdiploidy with greater than
50 chromosomes or a DNA index greater than 1.15. Among
ALL cases with hyperdiploidy greater than 50, the pattern
of chromosomal duplications, translocations, and deletions
was similar between the CD45' and CD45- cases (Table 2,
data for CD45+ cases not given). The region of the CD45
locus, 1q32: was duplicated in three of 25 CD45- and six of
42 CD45' cases with greater than 50 chromosomes (P = 1.0).
No correlation by univariate analysis was found between
CD45 antigen expression and age, sex, race, hepatomegaly,
splenomegaly, hemoglobin, platelet count, leukemic blast
morphology (FAB criteria), or presence of chromosomal
translocation (data not shown).
Because all CD45- cases were B-lineage leukemia, similar comparisons with presenting features were made after
excluding cases of TALL (Table 1). The absence of CD45
expression was still significantly associated with lower
serum LDH levels, leukemic cell hyperdiploidy with greater
than 50 chromosomes, and a DNA index greater than 1.15.
In fact, an inverse linear correlation between CD45 expression and DNA index could be shown (Fig 2).
At a median follow-up time of 2.7 years, patients with
CD45- blasts tended to have a more favorable outcome
than did those with CD45' blasts (18/19 v 86/111 patients
remain event-free survivors, P = .09). Because of the wide
range of CD45 levels, we determined whether the degree of
antigen expression might correlate more closely with clinical features and outcome. Patients were divided into three
groups as defined by CD45 positivity (group I, <20%;
group 11, 20% to 89%; group 111, 290%). Leukemic cell
hyperdiploidy with greater than 50 chromosomes (or DNA
index > 1.15) was found in 78% (56%), 28% (22%), and 9%
(6%) of groups I, 11,111(P values < .0001 in both comparisons). Prognosis clearly worsened as the level of CD45
expression increased (P = .03, Fig 3), with the majority of
treatment failures occurring in the group with greater than
or equal to 90% positivity. However, in multivariate analysis, the prognostic impact of CD45 expression lessened
substantially after adjustment for DNA index (P = .07).
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BEHM ET AL
1014
Fig 2. A smoothed, isotonic plot showing an inverse relationship
between levels of CD45 expression and DNA index of cases of
B-lineageALL.
DISCUSSION
CD45 antigen expression was undetectable on lymphoblasts in 13% of newly diagnosed childhood ALL cases. Our
results corroborate the observations of others showing that
some cases of lymphoma or acute leukemia or leukemic cell
lines may lack CD45.2“31However, given the ubiquitous
expression of this antigen on normal leukocytes and their
precursors, the relatively high frequency of CD45 negativity
in this study was unexpected. Although different isoforms
of CD45 may be expressed on hematopoietic cells: the
HLe-1 (clone 2D1) monoclonal antibody used in this study
detects the framework epitope common to all members of
the CD45 antigen family (CD45, CD45RA, CD45RB,
CD45RO) .“J’
Another intriguing finding was that all CD45- cases were
Fig 3. Comparison of event-free survival (EFS) of patients by level
of leukemic cell CD45 expression. A significantly worse outcome was
evident for patientswith z 90% CD45 positivity.Tick marks represent
patients still at risk of failure.
of the B-cell lineage. Even among CD45’ cases, expression
of the antigen was higher in T- than in B-lineage cases.
During the course of normal B-cell development and
differentiation, CD34 antigen expression progressively declines, while the expressions of CD45, CD20, and cytoplasmic immunoglobulins increase.’”% In this study, there was
an inverse correlation between CD34 and CD45 antigens,
as expected. However, a disproportionately high percentage of CD45- cases (12/32) had cytoplasmic b-immunoglobdin. Moreover, there was an inverse relationship between
CD45 and CD20 antigen expression, contrary to findings in
normal B-cell de~elopment?’.’~These results support the
contention that most B-lineage leukemias exhibit “developmental asynchrony” as compared with their normal counterpart~.~~,~~
Perhaps more interesting is the association between the
lack of or low CD45 antigen expression and the presence of
favorable presenting features of childhood ALL, including
low leukocyte counts and serum LDH levels, leukemic cell
hyperdiploidy with greater than 50 chromosomes, and a
DNA index greater than 1.15?7 The low or absent CD45
expression was marginally associated with a good prognosis
(P = .09). However, when cases were analyzed according to
the degree of CD45 expression, a significant correlation
with treatment outcome emerged. Similarly, in a limited
study of childhood and adult ALL, Caldwell et al’8 also
suggested an inverse relationship between quantitative
CD45 expression and therapeutic outcome. In their study,
patients with the least intensely staining lymphoblasts
appeared to have a more favorable response to therapy.
That CD45 expression lost prognostic significance in the
multivariate analysis is not surprising, since it is closely
correlated with leukemic cell ploidy and DNA content,
which are among the factors with the strongest prognostic
impa~t.3~
The biologic basis for CD45- blasts in a significant
proportion of B-lineage ALL cases is not clear from our
analyses. A possible explanation is that CD45- B-precursor
cells do in fact express the antigen, but at surface densities
too low for detection by flow cyt~metry.~’
However, lymphoblasts from our CD45- cases did not have detectable CD45
antigen when studied by the sensitive alkaline phosphatase
anti-alkaline phosphatase technique (unpublished data);
studies to identify the mRNA for this glycoprotein are
being performed. More difficult to reconcile is the association of hyperdiploidy and low expression of detectable
CD45. One possibility is that the cellular cytoskeletal
proteins that anchor the CD45 antigen39are also important
in orderly cell mitosis, so that defective skeletal proteins, as
might be found in leukemic cells, would result in both
hyperdiploidy and loss of CD45 in some cases of ALL.
In conclusion, we have shown that 13% of cases of newly
diagnosed childhood ALL lack CD45 antigen expression
and that these cases are of B lineage. We have further
demonstrated a significant inverse relationship between
leukemic blast CD45 antigen expression and blast cell
ploidy and clinical outcome. Further studies are needed to
define the functional basis for our observation that CD45cases tend to be hyperdiploid.
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CD45 EXPRESSION IN ALL
1015
REFERENCES
1. Omary MB, Trowbridge IS, Battifora HA: Human homologue of murine T200 glycoprotein. J Exp Med 152842,1980
2. Dalchau R, Kirkley J, Fabre Jw: Monoclonal antibody to a
human leukocyte-specificmembrane glycoprotein probably homologous to the leukocyte-common (L-C) antigen of the rat. Eur J
Immunol10:737,1980
3. Thomas M L The leukocyte common antigen family. Annu
Rev Immunol7:339,1989
4. Thomas ML, Barclay AN, Gagnon J, Williams A F Evidence
from cDNA clones that the rat leukocyte-common antigen (T200)
spans the lipid bilayer and contains a cytoplasmic domain of 80,000
M,. Cell 4133,1985
5. Ralph SJ, Thomas ML, Morton CC, Trowbridge IS: Structural variants of human T200 glycoprotein (leukocyte-common
antigen). EMBO J 61251,1987
6. Barclay AN, Jackson DI, Willis AC, Williams AF: Lymphocyte specific heterogeneity in the rat leucocyte common antigen
(T200) is due to differences in polypeptide sequences near the
NH,-terminus. EMBO J 6:1259,1987
7. Streuli M, Hall LR, Saga Y, Schlossman SF, Saito H:
Differential usage of three exons generates at least five different
mRNAs encoding human leukocyte common antigens. J Exp Med
166:1548,1987
8. Streuli M, Morimoto C, Schrieber M, Schlossman SF, Saito
H: Characterization of CD45 and CD45R monoclonal antibodies
using transfected mouse cell lines that express individual human
leukocyte common antigens. J Immunol141:3910,1988
9. Hall LR, Streuli M, Schlossman SF, Saito H: Complete
exon-intron organization of the human leukocyte common antigen
(CD45) gene. J Immunol141:2781,1988
10. Pulido R, Cebrian M, Acevedo A, de Landazuri MO,
Sanchez-Madrid F: Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities. J Immunol
140:3851,1988
11. Cobbold S, Hale G, Waldmann H: Non-lineage, LFA-1
family, and leucocyte common antigens: Newly and previously
defined clusters, in McMichael AJ (ed): Leucocyte Typing 111.
Oxford, UK, Oxford, 1987, p 796
12. Schwinzer R: Cluster report: CD45/CD45R, in Knapp W, et
a1 (eds): Leukocyte Typing IV. Oxford, Oxford, 1989, p 628
13. Charbonneau H, Tonks NK, Walsh KA, Fischer EH: The
leukocyte common antigen (CD45): A putative receptor-linked
protein tyrosine phosphatase. Proc Natl Acad Sci USA 85:7182,
1988
14. Tonks NK, Charbonneau H, Diltz CD, Fischer EH, Walsh
KA:Demonstration that the leukocyte common antigen CD45 is a
protein tyrosine phosphatase. Biochemistry 278695,1988
15. Ostergaard HL, Shackelford DA, Hurley TR, Johnson P,
Hyman R, Sefton BM, Trowbridge IS: Expression of CD45 alters
phosphorylation of the lck tyrosine protein kinase in murine
lymphoma T cell lines. Proc Natl Acad Sci USA 86:8959,1989
16. Mustelin T, Coggeshall KM, Aftman A Rapid activation of
the T-cell tyrosine protein kinase pp56Ickby the CD45 phosphotyrosine phosphatase. Proc Natl Acad Sci USA 86:6302,1989
17. Pingel JT, Thomas ML: Evidence that the leukocytecommon antigen is required for antigen-induced T lymphocyte
proliferation. Cell 58:1055, 1989
18. Rivera GK, Raimondi SC, Hancock ML, Behm FG, Pui
C-H, Abromowitch M, Mirro J Jr, Ochs JS, Look AT, Williams DL,
Murphy SB, Dahl GV, Kalwinsky DK, Evans WE, Kun LE, Simone
J, Crist WM: Improved outcome in childhood acute lymphoblastic
leukemia with reinforced early treatment and rotational combination chemotherapy. Lancet 337:61,1991
19. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton
DAG, Gralnick HR, Sultan C Proposals for the classification of
the acute leukaemias. French-American-British (FAB) cooperative group. Br J Haematol33:451, 1976
20. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton
DA, Gralnick HR, Sultan C The morphological classification of
acute lymphoblasticleukaemia: Concordance among observers and
clinical correlations. Br J Haematol47:553,1981
21. Williams DL, Harris A, Williams KJ, Brosius MJ, Lemonds
W A direct bone marrow chromosome technique for acute
lymphoblasticleukemia. Cancer Genet Cytogenet 13:239,1984
22. ISCN (1985): An international system for human cytogenetic nomenclature, in Harnden DG, Klinger HP (eds): published
in collaboration with Cytogenet Cell Genet (Basel, Switzerland,
Karger, 1985); also Birth Defects: Original Article Series, vol 21
(l), New York, NY, March of Dimes Birth Defects Foundation,
1985
23. Look AT, Roberson PK, Williams DL, Rivera G, Bowman
WP, Pui C-H, Ochs J, Abromowitch M, Kalwinsky D, Dahl GV,
George S, Murphy SB: Prognostic importance of blast cell DNA
content in childhood acute lymphoblastic leukemia. Blood 65:1079,
1985
24. Friedman J, Tibshirami R: The monotine smoothing of
scatter-plots. Technometrics 26:243,1984
25. Kaplan EL, Meier P: Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457,1958
26. Borowitz MJ, Stevanovic G, Gottfried M: Differential diagnosis of undifferentiated malignant tumors with monoclonal antibody T29/33. Hum Pathol15:928,1984
27. Ritter MA, Sauvage CA, Pegram SM, Myers CD, Dalchau
R, Fabre JW:The human leucocyte-common (LC) molecule:
Dissection of leukaemias using monoclonal antibodies directed
against framework and restricted antigenic determinants. Leuk
Res 9:1249,1985
28. Bernier V, Azar HA: Filiform large-cell lymphomas: An
ultrastructural and immunohistochemical study. Am J Surg Pathol
11:387,1987
29. Wick RW: Leukocyte common antigen expression in lymphomas. Arch Pathol Lab Med 112:867,1988 (letter)
30. de Mascarel A, Merlio J-P, Coindre J-M, Goussot J-F,
Broustet A Gastric large cell lymphoma expressing cytokeratin but
no leukocyte common antigen. Am J Clin Pathol91:478,1989
31. Bradstock KF, Janossy G, Pizzolo G, Hoflbrand AV, McMichael A, Pilch JR, Milstein C, Beverley P, Bollum FJ: Subpopulations of normal and leukemic human thymocytes: An analysis
with the use of monoclonal antibodies. J Natl Cancer Inst 65:33,
1980
32. Shah VO, Civin CI, Loken M R Flow cytometric analysis of
human bone marrow. IV. Differential quantitative expression of
T-200 common leukocyte antigen during normal hemopoiesis. J
Immunol140:1861,1988
33. Civin CI, Banquerigo ML, Strauss LC, Loken MR: Antigenic analysis of hematopoiesis. VI. Flow cytometric characterization of My-10-positive progenitor cells in normal human bone
marrow. Exp Hematol15:10,1987
34. Loken MR, Shah VO, Dattilio KL, Civin CI: Flow cytometric analysis of human bone marrow. 11. Normal B lymphocyte
development. Blood 701316,1987
35. Humitz CA, Loken MR, Graham ML, Karp JE, Borowitz
MJ, Pullen DJ, Civin CI: Asynchronous antigen expression in B
lineage acute lymphoblastic leukemia. Blood 72:299,1988
36. Borowitz MJ, Civin CI, Behm FG, Falletta JM, Shuster J,
Hurwitz CA, Carroll AJ, Look T, Pullen DJ, Crist WM: Pheno-
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1016
types encountered in B-lineage acute lymphoblastic leukemia
(ALL)do not reflect stages of normal B-cell differentiation. A
Pediatric Oncology Group study. Mod Pathol l:llA, 1988 (abstr)
37. Pui C-H, Crist WM: High risk lymphoblastic leukemia in
children: Prognostic factors and management. Blood Rev 1:25,
1987
BEHM ET AL
38. Caldwell CW, Patterson WP, Hakami N Alterations of
HLe-1 (T200) fluorescence intensity on acute lymphoblastic leukemia cells may relate to therapeutic outcome. Leuk Res 11:103,1987
39. Suchard SJ, Bourguignon LYW: Further characterization of
a fodrin-containing transmembrane complex from mouse T-lymphoma cells. Biochem Biophys Acta 896:35,1987
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1992 79: 1011-1016
Lack of CD45 antigen on blast cells in childhood acute lymphoblastic
leukemia is associated with chromosomal hyperdiploidy and other
favorable prognostic features [see comments]
FG Behm, SC Raimondi, MJ Schell, AT Look, GK Rivera and CH Pui
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