[CANCER RESEARCH 40. 4048-4052, November 1980] 0008-5472/80/0040-OOOOS02.00 Myeloblastic and Lymphoblastic Markers in Acute Undifferentiated Leukemia and Chronic Myelogenous Leukemia in Blast Crisis1

Kenneth H. Shumak,2 Michael A. Baker, Robert N. Taub, Mary Sue Coleman,3 and the Toronto Leukemia Study Group4

Department of Medicine, Toronto General [K. H. S.] and Toronto Western [M. A. B.J Hospitals, University of Toronto, Toronto. Ontario M5G 1L7. Canada: Department of Medicine. Medical College of Virginia, Richmond, Virginia 23298 [R. N. T.], and the Department of Biochemistry. University of Kentucky. Lexington, Kentucky 40506 [M. S. C.¡

ABSTRACT difficult cases, special cytochemical stains may be helpful but there remains a group, comprising up to 10% of patients with Blast cells were obtained from 17 patients with acute undif- acute leukemia (10), in which morphology and special stains ferentiated leukemia and 13 patients with chronic myelogenous are inadequate to classify the leukemia. leukemia in blast crisis. The blasts were tested with anti-i serum Several markers have been identified which distinguish my in cytotoxicity tests and with antisera to myeloblastic leukemia- eloblastic from lymphoblastic leukemia (2, 7, 23-25), and associated antigens in immunofluorescence tests. The terminal some of these have been used in an attempt to classify, as deoxynucleotidyl transferase (TDT) content of the blasts was myeloblastic or lymphoblastic, AUL5 (8, 13, 21, 25) and CML also measured. Lymphoblasts react strongly with anti-i, do not in blast crisis (12, 15, 17, 19, 20, 22). With each marker, react with anti-myeloblast serum, and have high levels of TDT; blasts from patients with AUL or CML in blast crisis react either myeloblasts react weakly with anti-i, do react with anti-myelo like myeloblasts or like lymphoblasts, but there is limited infor blast serum, and have very low levels of TDT. Of the 17 patients mation comparing the classification of these blasts by different with acute undifferentiated leukemia, there were six with blasts markers (19, 20). which reacted like lymphoblasts, six with blasts which reacted Several studies suggest that classification of blasts in pa like myeloblasts, and five with blasts bearing different combi tients with AUL or CML in blast crisis may be of value in nations of these lymphoblastic and myeloblastic markers. Eight selecting optimal therapy and predicting prognosis (3, 20, 22). of the 11 patients with lymphoblastic or mixed lymphoblastic- However, the accuracy of the various markers in classifying myeloblastic markers, but only one of the six with myeloblastic blasts as myeloblastic or lymphoblastic has been established markers, achieved complete or partial remission in response to by studies of morphologically typical AM L and ALL. Since there therapy. Thus, in acute undifferentiated leukemia, classification are no absolute criteria by which to assess the accuracy of of blasts with these markers may be of prognostic value. classification as myeloblastic or lymphoblastic of blasts from Of the 13 patients with chronic myelogenous leukemia in patients with AUL or CML in blast crisis, it is important to blast crisis, the markers were concordant (for myeloblasts) in determine whether their classification by different markers only two cases. Three of the 13 patients had TDT-positive agrees. The possibility that such concordance may not always blasts, but the reactions of these cells with anti-i and with anti- occur, at least in patients with CML in blast crisis, is suggested myeloblast serum differed from those seen with lymphoblasts by the observation that some of these patients may have, at from patients with acute lymphoblastic leukemia. Although the the same time, some cells reacting like myeloblasts and others cell involved in "lymphoid" blast crisis of chronic myelogenous reacting like lymphoblasts (19). leukemia is similar in many respects to that involved in acute The present study was done to compare the classification by lymphoblastic leukemia, these cells are not identical. tests for 3 different markers (i antigen, myeloblastic leukemia- associated antigen, TDT) of blasts from patients with AUL and INTRODUCTION from patients with CML in blast crisis.

Conventional morphological criteria (5) usually enable one to MATERIALS AND METHODS classify acute leukemia as myeloblastic or lymphoblastic. In AUL. Patients with acute leukemia were considered to have AUL when their attending hematologists were unable to classify

' Supported by Grant MA-5069 from the Medical Research Council of Canada; the leukemia as AML or ALL using conventional morphological Grant 285 from the Ontario Cancer Treatment and Research Foundation, the criteria (5). All patients were adults except Patients 6 and 17 National Cancer Institute of Canada; Grant CA 19492 from the NIH, and Grant who were 10 and 12 years old, respectively. The lack of CM 67038 from the National Cancer Institute. 2 To whom requests for reprints should be addressed, at Division of Hematol- diagnostic morphological features was confirmed by examina ogy. Toronto General Hospital, 101 College St.. Toronto. Ontario. Canada M5G tion of blood and bone marrow films from these patients by a 1L7. hematological pathologist who was not otherwise involved in 3 Recipient of Research Cancer Award K04 CA 00494. * The following are contributing members of the Toronto Leukemia Study this study. Cytochemical stains had been done on specimens Group: Doctors Hospital, Dr. Harvey Silver; Mississauga Hospital, Dr. Michael from some of these patients, but the results of these studies King; Mount Sinai Hospital. Dr. Dominic Amato: Oshawa General Hospital. Dr. Hak Chiù; St. Michael's Hospital. Dr. Bernadette Garvey; St. Joseph's Hospital. were not used to include or exclude any patient. Dr. Murray Davidson, Dr. H. James Watt; Toronto General Hospital, Dr. John CML in Blast Crisis. Patients with CML were considered to Crookston, Dr. William Francombe. Dr. Gerald Scott. Dr. Kenneth Shumak; Toronto Western Hospital, Dr. Michael Baker, Dr. David Sutton, Dr. James G. 5 The abbreviations used are: AUL, acute undifferentiated leukemia; CML, Watt; York Finch Hospital, Dr. Sam Berger. chronic myelogenous leukemia: TDT. terminal deoxynucleotidyl transferase; ALL. Received March 19, 1980; accepted August 12, 1980. acute lymphoblastic leukemia; AML, acute myeloblastic leukemia.

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Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1980 American Association for Cancer Research. Markers in Undifferentiated Leukemia be in blast crisis when 30% or more of the leukocytes in their ringed with bright surface dots using the Ploem vertical illumi peripheral blood were blasts (9). All patients were adults and nator (1). were included for study regardless of whether the CML was Sera used in this study showed a mean reactivity with known Philadelphia chromosome positive or negative. myeloblasts of 59 ±16% (S.D.) of cells per sample, whereas Cells. Blasts from patients with AUL were collected for study reactivity with known lymphoblasts was 4 ± 2%. Based on before the institution of any chemotherapy. Blasts from patients these previous tests, a minimum of 30% of cells fluorescing is with CML in blast crisis were also collected before starting required to identify blasts as myeloblasts. chemotherapy for the crisis, but most of these patients had TDT Assays. The technique for assay of TDT has been received myleran during the chronic phase of their disease. described previously (11 ). Nucleated cell suspensions at a Blasts from all patients were obtained from the peripheral density of 1 to 2 x 108 cells/ml in 0.25 M phosphate buffer, blood. Normal lymphocytes were obtained from the blood of pH 7.5, containing 1 HIM mercaptoethanol were sonicated 4 healthy adults. times in 15-sec bursts, with cooling. The sonicate was centri- Defibrinated blood was applied to a Hypaque-Ficoll gradient, fuged at 100,000 x g for 60 min, and the resulting supernatant and the interface layer was harvested (6). With one exception was assayed for TDT. Assay mixtures contained, at final con (Patient 17, 54% blasts), the final leukemic cell populations centration, 0.2 M potassium cacodylate buffer (pH 7.5), 1 mM studied contained at least 80% blasts and most contained [3H]dGTP (specific activity, 120 cpm/pmol), 0.02 mM >95% blasts. oligo[d(pA)5o], 8 mM MgCI2, 1 mM mercaptoethanol, and 50 mM Cytotoxicity Tests with Anti-i. Anti-i Den. was kindly pro phosphate. One unit of TDT equals 1 nmol of nucleotide polym vided by Dr. D. H. Cowan (Sunnybrook Medical Centre). This erized per hr at 35°.Specific activities are expressed as units/ serum distinguishes lymphoblasts from myeloblasts in that it is 108 cells. as cytotoxic to lymphoblasts as to normal lymphocytes (50% Using this assay, blasts from patients with ALL contain >20 kill in dilutions up to approximately 1:1280 to 1:2560) but units/108 cells, whereas blasts from patients with AML contain much less cytotoxic to myeloblasts (50% kill in dilutions up to <9 units/108 cells (15). approximately 1:10 to 1:20) (25). In cytotoxicity tests, anti-i Den. and rabbit complement were added to cells, and the RESULTS mixtures were incubated at 4°for 30 min and then at 25°for another 30 min (26). Cytotoxicity was assayed by trypan blue AUL. Blasts from 17 patients with AUL were studied. Blasts exclusion. from 12 patients were tested with anti-i and anti-myeloblast Fluorescence Tests with Anti-Myeloblast Serum. Anti-mye- serum and were assayed for TDT; blasts from 3 patients were loblast sera were obtained from patients with AML in remission tested with anti-i and anti-myeloblast serum but were not as receiving immunotherapy with Bacillus Calmette-Guérìnand sayed for TDT; blasts from the other 2 patients were tested irradiated allogeneic leukemic cells (1). Cells were tested by with anti-i and assayed for TDT but not tested with anti-mye incubation with antiserum at 4°for 30 min. Suspensions were loblast serum. washed in medium containing 0.01% sodium azide and were The results of these studies and clinical information about incubated at 4°for another 30 min with fluorescein-conjugated the patients are summarized in Table 1. Of the 12 patients in goat anti-human IgG. Cells were counted as positive when whom all 3 markers were studied, the blasts reacted as mye-

Table 1 i antigen, myeloblastic leukemia-associated antigen, and TDT level of blasts from patients with AUL

cence with toxic anti-mye level ity by loblast se- (units/ 10s anti-ia2,5602.5602.5602.5605.1206402010<10<10<10102.56010.240201020Fluoresb PatientLymphoblast rum713<5NO18<59272606080ND7570217<5TDTcells)85.63.72564.7NDND0000ND022.48.99.501.9TreatmentresponseV, and (mos.)69In NRCV,P -»NR. Adria. ara-C — 123456Myeloblastmarkers CRDNR.P —•NR.Adria, ara-C — CRV, ara-C— mos.InCR at 4 P ->CRDNR, mos15InCR at 24 PRV, ara-C — CRV.P, asparaginase —• mos.5059153159214InCR at 24

789101112"Mixedmarkers PRDNR,P —NR. DNR, ara-C — NRV, ara-C — NRV,P —NR. Adria, ara-C — P-,NRV, NRDNR,P-» NR, Adria, ara-C — NRV, ara-C -•

" markers 1314151617Cyto P—CRV, NRDNR,Adria. ara-C, Cyclo -» NRAdria.ara-C — PRV, ara-C -> ara-C, Cyclo -»CRSurvival CR at 6 mos. Reciprocal of highest dilution of anti-i killing 50% of the cells. Percentage of brightly fluorescing cells observed after sequential incubation with anti-myeloblast serum and fluorescein-labeled goat anti-human IgG. c V, vincristine; P. prednisone; NR, no remission; Adria. Adriamycin; ara-C. 1-/i-o-arabinofuranosylcytosine; CR. complete remission; DNR, daunorubicin; ND, not done; PR, partial remission; Cyclo, cyclophosphamide.

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Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1980 American Association for Cancer Research. K. H. Shumak et al. loblasts in all tests in 4 cases and as lymphoblasts in all tests found in 7 of the 12 patients who had cytogenetic studies ¡n2cases. One other patient (Patient 2), classified as lympho- done. blastic in tests with anti-i and anti-myeloblast serum, had 3.7 Blasts from 9 patients were tested with anti-i and anti-mye units TOT per 108 blasts, a higher level than is found in blasts loblast serum and were assayed for TDT, blasts from 3 patients from most patients with AML but less than what is found in were tested with anti-i and anti-myeloblast serum but TDT patients with typical ALL. In the other 5 cases (Patients 13 to assays were not done; blasts from the other patient were tested 17), the classification by one of the markers was different from with anti-i and assayed for TDT but were not tested with anti- that by the other 2 markers. myeloblast serum. Of the 5 patients tested for only 2 of the 3 markers, there The results of these studies and clinical information about was definite concordance in 4 (lymphoblastic markers in 2, the patients are shown in Table 2. The markers were concord myeloblastic markers in 2); in the other patient (Patient 4), a ant (for myeloblasts) in only 2 of these 13 cases of blast crisis. lymphoblastic reaction in tests with anti-i was associated with Moreover, of these 2 cases, in one (Patient 18), only 2 of the a borderline TDT level of 4.7 units/10s cells. 3 markers (i antigen and myeloblast antigen) were studied; in Including the 2 patients (Patients 2 and 4) with borderline the other (Patient 19), the reaction with anti-myeloblast serum TDT levels, there were therefore 6 patients with AUL which was was very weak. classified as lymphoblastic in tests for these markers. Four Three patients (Patients 19, 28, and 29) did not receive achieved a complete remission and one achieved a partial chemotherapy for their blast crisis. Of the remaining 10 pa remission in response to chemotherapy. The mean survival of tients, 4 (Patients 22, 24, 25, and 27) responded to chemo these patients with lymphoblastic markers is 13+ months therapy and survived for a mean of 9 months from the diagnosis (Patients 3, 4, and 6 are still alive and in remission at 4, 24, of crisis, and 6 did not respond, surviving a mean of just less and 24 months, respectively). None of the 6 patients whose than 4 months from the diagnosis of crisis. leukemia was myeloblastic by these markers achieved a com plete remission, but one did achieve a partial remission in response ,to therapy. Mean survival of patients in this group DISCUSSION was 4 months. Two of the 5 patients with both myeloblastic and lympho The relationship of AUL to morphologically typical AML and blastic markers achieved a complete remission, and one ALL is unclear. Unlike blasts from patients with the common achieved a partial remission. Mean survival of patients in this variety of ALL, blasts from patients with AUL do not react with group is 9+ months (Patient 17 is still alive and in remission at anti-ALL serum, nor do they possess T-lymphocyte markers 6 months). which would suggest a relationship to the less common T-cell CML in Blast Crisis. Blasts were studied from 12 patients variety of ALL (14). However, TDT is detected in the blasts of with CML in blast crisis and from another patient who had had some patients with AUL (13, 14), and in these TDT-positive polycythemia rubra vera progressing to myelofibrosis and, cases there is therefore a definite relationship to the common eventually, to blast cell leukemia. The Ph1 chromosome was non-T, non-B, and the less common T-cell type of ALL, both of

Table 2 i antigen, myeoblastic leukemia-associated antigen, and TDT level of blasts from patients with CML in blast crisis

cence with anti- toxicitybyanti-ia1040202560101020<10<10<10256020<10Fluoresmyelo level(units/10s blastserum"762052102<5<5<5<5<5602NDTDT PatientMyeloblast cells)NDC059.3097.10074.40.890NDND0Ph1chromosomeNeg.Pos.Pos.Neg.Neg.Pos.Pos.Pos.Pos.Pos.Neg.Neg.NDTreatmentresponseV, and 819"Mixed" markers 1 ara-CAdria,P —NR. DNR, NRNo 6-MP -> therapyV,

markers 202122232425262728"2930Cyto- NRV.P, DNR — NRV,Adria, Cyclo— ara-C,Cyclo,P, DNR, Adria, 6TG. RV, Mtx -> P-.NRV, RV.P. DNR-. RDNR.P. DNR— NR6TG,Adria, 6TG— RNo ara-C — therapyNo therapyV, P, Adria, Cyclo —NRSurvival(mos.)359170.5852122 Reciprocal of highest dilution of anti-i killing 50% of the cells. Percentage of brightly fluorescing cells observed after sequential incubation with anit-myeloblast serum and fluorescein-labeled goat anti-human IgG. c ND. not done; Neg.. negative; V, vincristine; P, prednisone; NR, no response (blast crisis persisted); DNR, daunorubicin; ara-C, 1-/<-D-arabinofuranosylcytosine; Adria, Adriamycin; 6-MP, 6-mercaptopurine; Pos., positive; Cyclo. cyclophosphamide; 6TG, 6-thioguanine; Mtx. methotrexate; R, response. Blast crisis following polycythemia rubra vera and myelofibrosis.

4050 CANCER RESEARCH VOL. 40

Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1980 American Association for Cancer Research. Markers in Undifferentiated Leukemia which are TDT positive (11, 13, 14). If AUL arises in a pluri- found in blasts of some patients with CML in blast crisis. potential hematopoietic stem cell, it might be possible to dem Interestingly, these markers may be found in patients whose onstrate myeloid markers in at least some cases of AUL (for leukemia is morphologically myeloblastic as well as in those example, in those which are TDT negative). whose leukemia is morphologically lymphoblastic (20, 22). In the present study, blasts from patients with AUL were In tests for a variety of markers, including those associated tested for 3 markers which distinguish typical myeloblasts from with T- and B-cells as well as those characteristic of the typical lymphoblasts: the i antigen, detected in much smaller common non-T, non-B form of ALL, Janossy ef al. (16, 17, 20) amounts on myeloblasts than on lymphoblasts in cytotoxicity found no difference in the reactions of blasts from patients with tests with anti-i (25); myeloblastic leukemia-associated anti CML in "lymphoid" blast crisis and those of blasts from patients gens, detected on myeloblasts, but not on lymphoblasts in with common non-T, non-B ALL, leading them to suggest that fluorescence tests using serum from patients with AML in these diseases may arise from the same pluripotential stem remission who have received immunotherapy with Bacillus cells. Calmette-Guerin and irradiated allogeneic leukemic cells (1); In the present study, blasts from patients with CML in blast and TDT, found in high concentrations in lymphoblasts but not crisis were tested with anti-i and anti-myeloblast serum, and detectable, or detectable in very low concentration, in myelo their TDT level was assayed. Blasts from patients with ALL blasts (15). react strongly with anti-i (25) and do not react with anti-mye Those AUL blasts which contained TDT, had abundant sur loblast serum (1). By contrast, none of the 3 cases of TDT- face i antigen, and lacked the myeloblast antigen were consid positive blast crisis in the present study reacted strongly with ered to possess lymphoblast markers; those AUL blasts which anti-i and one (Patient 20) reacted with anti-myeloblast serum. lacked TDT, had very weak i antigen, and had readily detect The reaction with anti-myeloblast serum could have been due able myeloblast antigen were considered to possess myelo to the presence in this patient of a TDT-negative myeloid blast blast markers. Blasts with these markers in any other combi population, but this hypothesis does not account for the failure nation were considered to possess "mixed" markers. Within of the TDT-positive population in this patient and in the other this last group, blast populations which lack an expected patients to react with anti-i. marker (e.g., weak i antigen despite detectable TDT) should Thus, in CML in blast crisis, TDT-positive blasts differ from be distinguished from blast populations with an unexpected those in the ALL patients that we have tested previously. additional marker (e.g., myeloblast antigen as well as i antigen Although blasts from these ALL patients were not tested for T- and TDT). The lack of a marker may be due to inadequate cell markers or with anti-ALL serum, it is very likely (because maturation. However, maturation-dependent changes cannot of the high frequency among patients with ALL, of the non-T, explain the presence of markers of different lineages. In such non-B form) that at least some of the patients in these previous a case, either 2 populations (one lymphoid, one myeloid) of studies (1, 25) had non-T, non-B ALL. TDT-positive blasts in leukemic cells must be present or there is a single population patients who have CML in blast crisis are therefore probably with both lymphoid and myeloid markers. The former explana different from the blasts in the common non-T, non-B form of tion seems more likely since there is other evidence (in patients ALL, the difference most likely being one of maturation. The with CML in blast crisis) that more than one clone of cells may previous findings of Janossy ef al. (16, 17, 20) of a similarity be involved (12, 19). in the markers of these 2 types of blasts appear to have been In tests of blasts from 17 patients with AUL, the markers a function of the markers that they tested rather than an detected were those of myeloblasts in 6 cases, lymphoblasts indication of true identity. in 6 cases (including 2 classified as lymphoblastic in tests with The lack of reaction, in many of these patients, of anti- anti-i and anti-myeloblast serum, in which the TDT levels were myeloblast serum with blasts which were TDT negative and only marginally elevated), and "mixed" in the other 5 cases. weakly reacting with anti-i suggests that the cell involved in "myeloid" blast crisis is also less "mature" than the cell Of the 5 cases of AUL discordant for the myeloblastic and lymphoblastic markers tested, 2 (Patients 13 and 14) ex involved in typical AML. pressed both the i and myeloblast antigens as well as being In the present study, the variety of drug combinations used TDT positive. In the other 3 cases, the discordant markers for patients with AUL and for those with CML in blast crisis appear to reflect lack of maturation rather than mixed myeloid- makes it difficult to draw conclusions about the value of tests lymphoid differentiation. for i antigen, myeloblast antigen, and TDT in predicting the The finding that some patients with AUL have lymphoblastic response to therapy. However, among the patients with AUL, markers confirms the observations of Hoffbrand ef al. (14) and the remission rate was higher and mean survival was longer in those with lymphoblastic or "mixed" markers than in those Gordon ef al. (13). The findings that patients with AUL may also have myeloblastic markers, either alone or in combination with with myeloblastic markers, and a study using a standard treat lymphoblastic markers, and that still other patients with AUL ment protocol is warranted. may lack both the myeloblastic and lymphoblastic markers There was no consistent difference in the markers of the 4 studied support the hypothesis that AUL arises in a pluripoten- patients with CML in blast crisis who responded to treatment tial hematopoietic stem cell capable of expressing a variety of and the 6 who did not. The finding that 2 of the 4 responders lymphoid and myeloid markers. and only 1 of the 6 nonresponders were TDT positive suggests, Boggs suggested that, in some patients with CML who have as reported by others (20, 22), that had larger numbers of entered blast crisis, the crisis may be lymphoblastic rather than patients been studied a significantly better response rate might myeloblastic (4). This hypothesis was based on morphological have been observed in those patients who were TDT positive considerations but, more recently, the antigen detected by than in those who were TDT negative. Studies of additional anti-ALL serum (3, 17,18, 20) and TDT (1 2, 15, 22) have been patients are required to determine whether there is prognostic

NOVEMBER 1980 4051

Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1980 American Association for Cancer Research. K. H. Shumak et al. value ¡nclassifying CML in blast crisis by tests with anti-i and Terminal deoxynucleotidyl transferase (TdT). cytochemistry and membrane anti-myeloblast serum as well as by assays for TDT. receptors in adult acute leukemia. Blood, 52. 1079-1088, 1978. 14. Hoffbrand. A. V.. Ganeshaguru, K.. Janossy. G.. Greaves, M. F., Catovsky, D., and Woodruff, R. K. Terminal deoxynucleotidyl-transferase levels and ACKNOWLEDGMENTS membrane phenotypes in diagnosis of acute leukaemia. Lancet, 2. 520- 523, 1977. We wish to acknowledge the excellent technical assistance of Rose Rachke- 15. Hutton, J. J., and Coleman, M. S. Terminal deoxynucleotidyl transferase wich, Gordon Hyland, and Joy Hughes. We are also indebted to Dr. Dominic measurements in the differential diagnosis of adult leukaemias. Br. J. Hae Pantalony for reviewing blood and bone marrow films. matol.. 34. 447-456, 1976. 16. Janossy, G., Goldstone. A. H.. Capellaro, D., Greaves, M. F., Kulenkampff. J., Pippard, M., and Welsh. K. Differentiation linked expression of p28,33 REFERENCES (la-like) structures on human leukaemic cells. Br. J. Haematol.. 37. 391- 402, 1977. 1. Baker. M A.. Falk, J. A., and Taub, R. N. Immunotherapy of human acute 17. Janossy, G., Greaves, M. F., Revesz. T., Lister, T. A.. Roberts, M., Durrant, leukemia: antibody response to leukemia-associated antigens. Blood, 52. J., Kirk, B., Catovsky, D.. and Beard. M. E. J. Blast crisis of chronic myeloid 469-480, 1978. leukaemia. II. Cell surface marker analysis of "lymphoid" and "myeloid" 2. Baker, M. A., Ramachandar, K., and Taub, R. N. Specificity of heteroantisera cases. Br. J. Haematol.. 34: 179-192. 1976. to human acute leukemia-associated antigens. J. Clin. Invest., 54: 1273- 18. Janossy, G., Roberts, M.. and Greaves, M. F. 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Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1980 American Association for Cancer Research. Myeloblastic and Lymphoblastic Markers in Acute Undifferentiated Leukemia and Chronic Myelogenous Leukemia in Blast Crisis

Kenneth H. Shumak, Michael A. Baker, Robert N. Taub, et al.

Cancer Res 1980;40:4048-4052.

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