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Immunophenotypes

Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expression

Leukemia volume 15, pages 406–414 (2001)Cite this article

Abstract

The Philadelphia chromosome (Ph+) reflects a balanced reciprocal translocation between the long arms of chromosomes 9 and 22 [t(9;22)(q34;q11.2] involving the BCRand ABL genes. At present, detection of BCR/ABL gene rearrangements is mandatory in precursor-B-ALL patients at diagnosis for prognostic stratification and treatment decision. In spite of the clinical impact, no screening method, displaying a high sensitive and specificity, is available for the identification of BCR/ABL +precursor-B-ALL cases. The aim of the present study was to explore the immunophenotypic characteristics of precursor B-ALL cases displaying BCR/ABL gene rearrangements using multiple stainings analyzed by quantitative flow cytometry in order to rapidly (<1 h) identify unique phenotypes associated with this translocation. From the 82 precursor-B-ALL cases included in the study 12 displayed BCR/ABL gene rearragements, all corresponding to adult patients, four of which also displayed DNA aneuploidy. Our results show that BCR/ABL + precursor B-ALL cases constantly displayed a homogeneous expression of CD10 and CD34 but low and relatively heterogeneous CD38 expression, together with an aberrant reactivity for CD13. In contrast, this unique phenotype was only detected in three out of 70 BCR/ABL − cases. Therefore, the combined use of staining patterns for CD34, CD38 and CD13 expression within CD10-positive blast cells is highly suggestive of BCR/ABL gene rearrangements in adults with precursor B-ALL.

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References

  1. Rowley JD . A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Guiemsa staining Nature 1973 243: 290–293 (letter)

    Article  CAS  PubMed  Google Scholar 

  2. Rowley JD . Molecular genetics in acute leukaemia Leukemia 2000 14: 513–517

    Article  CAS  PubMed  Google Scholar 

  3. Sandbery AA, Morgan R, Kipp TJ, Hecht F . The Philadelphia (ph) chromosome in leukemia. II. Variant Ph translocations in acute lymphoblastic leukemia Cancer Res Cytogenet 1985 14: 11–21

    Article  Google Scholar 

  4. Melo JV . The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype Blood 1996 88: 2375–2384

    CAS  PubMed  Google Scholar 

  5. Saglio G, Guerrasio A, Rosso C, Zaccaria A, Tassinari A, Serra A, Rege-Cambrin G . New type of Bcr/Abl junction in philadelphia chromosome-positive chronic myelogenous leukemia Blood 1990 76: 1819–1824

    CAS  PubMed  Google Scholar 

  6. Fardel S, Kantarjian HM, Talpaz M, Estrov Z . Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia Blood 1998 91: 3995–4019

    Google Scholar 

  7. Hagemeijer A . Chromosome abnormalities in CML Clin Haematol 1987 1: 963–981

    CAS  Google Scholar 

  8. Gale RP, Canaani E . Review: the molecular biology of chronic myelogenous leukemia Br J Haematol 1985 60: 395–408

    Article  CAS  PubMed  Google Scholar 

  9. Bloomfield CD, Goldman AI, Alimena, Berger R, Borgstrom GH, Brandt L, Catovsky D, de la Chapelle A, Dewald GW, Gaison OM . Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia Blood 1986 67: 415–420

    CAS  PubMed  Google Scholar 

  10. Rieder H, Bonwetsch C, Janssen LA, Maurer J, Janssen JW, Schwartz S, Ludwig WD, Gassman W, Bartram CR, Thiel E, Loffler H, Gokbuget N, Hollzer D, Fonatsch C . High rate of chromosome abnormalities detected by fluorescence in situ hybridization using BCR and ABL probes in adult acute lymphoblastic leukemia Leukemia 1998 12: 1473–1481

    Article  CAS  PubMed  Google Scholar 

  11. Copelan EA, McGuire EA . The biology and treatment of acute lymphoblastic leukemia in adults Blood 1995 85: 1151–1168

    CAS  PubMed  Google Scholar 

  12. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV . Philadelphia positive acute lymphoblastic leukaemia in adults – age distribution, BCR breakpoint and prognostic significance Leukemia 1991 5: 196–199

    CAS  PubMed  Google Scholar 

  13. Annino L, Ferrari A, Cedrone M, Giona F, Lo Coco F, Meloni G, Arcese W, Mandelli F . Adult Philadelphia-chromosome-positive acute lymphoblastic leukaemia: experience of treatments during a 10-year period Leukemia 1994 8: 664–667

    CAS  PubMed  Google Scholar 

  14. Secker-Walker LM, Pentrice HG, Durrant J, Richards S, Hall E, Harrison G . Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA Br J Haematol 1997 96: 601–610

    Article  CAS  PubMed  Google Scholar 

  15. Pui CH, Crist WM, Look T . Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukaemia Blood 1990 76: 1449–1463

    CAS  PubMed  Google Scholar 

  16. Pui CH, Evans WE . Acute lymphoblastic leukemia New Engl J Med 1998 339: 605–615

    Article  CAS  PubMed  Google Scholar 

  17. Götz G, Weh HJ, Walter TA, Kuse R, Kolbe K, Dolken G, Hellrieger KP, Hoelzer D, Hossfeld DK . Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic Ann Hematol 1992 64: 97–100

    Article  PubMed  Google Scholar 

  18. Westbrook CA, Hooberman AL, Spino C, Dodge RK, Laison RA, Davey F, Wurster-Hill DH, Sobol RE, Schiffer C, Bloomfield CD . Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a cancer and leukemia group B study (8762) Blood 1992 80: 2983–2990

    CAS  PubMed  Google Scholar 

  19. Roberts WM, Rivera GK, Raimondi SC, Santana VM, Sandlund JT, Crist WM, Pui CH . Intensive chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukemia Lancet 1994 343: 331–332

    Article  CAS  PubMed  Google Scholar 

  20. Faderl S, Kantarjian HM, Thomas DA, Cortes J, Giles F, Pierce S, Albitar M, Estrov Z . Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia Leuk Lymphoma 2000 36: 263–273

    Article  CAS  PubMed  Google Scholar 

  21. Brisco MJ, Sykes PJ, Dolman G, Neoh SH, Hughes E, Peng LM, Tauro G, Ekert H, Toogood I, Bradstock K, Morley AA . Effect of the Philadelphia chromosome on minimal residual disease in acute lymphoblastic leukemia Leukemia 1997 11: 1497–1500

    Article  CAS  PubMed  Google Scholar 

  22. Jennings CD, Foon KA . Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy Blood 1997 90: 2863–2892

    CAS  PubMed  Google Scholar 

  23. Ong ST, Larson RA . Current management of acute lymphoblastic leukemia in adults Oncology 1995 9: 433–442

    CAS  PubMed  Google Scholar 

  24. Campana D, Pui CH . Detection of minimal residual disease in acute leukemia: methodologic advanced and clinical significance Blood 1995 85: 1416–1434

    CAS  PubMed  Google Scholar 

  25. Ciudad J, San Miguel JF, López-Berges MC, Vidriales B, Valverde B, Ocqueteau M, Mateos G, Caballero MD, Hernández J, Moro MJ, Mateos Mv, Orfao A . Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia J Clin Oncol 1998 16: 3774–3781

    Article  CAS  PubMed  Google Scholar 

  26. Orfao A, Schmitz G, Brando B,. Ruiz-Arguelles A, Basso G, Braylan R, Rothe G, Lacombe F, Lanza F, Papa S, Lucio P, San Miguel JF . Clinically useful information provided by the flow cytometric immunophenotyping of hematological malignancies: current status and future directions Clin Chem 1999 45: 1708–1717

    CAS  PubMed  Google Scholar 

  27. Orfao A, Ciudad J, Almeida J, San Miguel JF . Residual disease detection of leukemia. In: Stewart CC, Nicholson JKA (eds) Immunophenotyping Wiley-Liss: New York 2000 pp 239–259

    Google Scholar 

  28. Borowitz MJ, Rubnitz J, Nash M, Pullen DJ, Camitta B . Surface antigen phenotype can predict TEL-AML1 rearrangement in childhood B-precursor ALL: a Pediatric Oncology Group study Leukemia 1998 12: 1764–1770

    Article  CAS  PubMed  Google Scholar 

  29. Borowitz MJ, Hunger SP, Carroll AJ, Shuster JJ, Pullen DJ, Steuber CP, Cleary ML . Predictability of the t(1;19)(q23;p13) from surface antigen phenotype: implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis. A Pediatric Oncology Group study Blood 1993 82: 1086–1091

    CAS  PubMed  Google Scholar 

  30. De Zen L, Orfao A, Cazzaniga G, Maziero L, Cocito MG, Spinelli M, Rivolta A, Biondi A, Zanesco L, Basso G . Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. ETV6/AML1 ALLs identification Leukemia 2000 14: 1225–1231

    Article  CAS  PubMed  Google Scholar 

  31. Tritz D, Pettigrew A, Talkington S, Smith L, Jennings CD . Association of CD15 expression and 11q23 translocation in acute leukemias Mol Pathol 1995 8: 122–129

    Google Scholar 

  32. Pui CH . Acute leukemias with the t(4;11)(q21;q23) Leuk Lymphoma 1992 7: 173–179

    Article  CAS  PubMed  Google Scholar 

  33. Pui CH, Raimondi SC, Head DR, Schell MJ, Rivera GK, Mirro J Jr, Crist WM, Behm FG . Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse Blood 1991 78: 1327–1337

    CAS  PubMed  Google Scholar 

  34. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van't Veer MB . Proposals for the immunological classification of acute leukemias. European Group for the immunological characterization of leukemias (EGIL) Leukemia 1995 9: 1783–1786

    CAS  PubMed  Google Scholar 

  35. Orfao A, Ciudad J, López-Berges MC, López A, Vidriales B, Caballero MD, Valverde B, González M, San Miguel JF . Acute lymphoblastic leukemia (ALL): detection of minimal residual disease (MRD) at flow cytometry Leuk Lymphoma 1994 13: (Suppl. 1) 87–90

    Article  PubMed  Google Scholar 

  36. San Miguel JF, García-Sanz R, González M, Moro MJ, Hernández JM, Ortega F, Borrega D, Carnero M, Casanova F, Jimenez R . A new staging system for multiple myeloma based on the number of S-phase plasma cells Blood 1995 85: 448–455

    CAS  PubMed  Google Scholar 

  37. Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Anal Biochem 1987 162: 156–159

    Article  CAS  PubMed  Google Scholar 

  38. van Dongen JJ, Macintyre EA, Gabert JA, Delabesse F, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dolti G, Griesinger F, Parreira A, Gameiro A, Diaz MG, Malec M, Langerak AW, San Miguel JF, Biondi A . Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease Leukemia 1999 13: 1901–1928

    Article  CAS  PubMed  Google Scholar 

  39. García Isidoro M, Tabernero MD, García JL, Najera ML, Hernández JM, Wiegant J, Raap A, San Miguel J, Orfao A . Detection of the Mbcr/abl translocation in chronic myeloid leukaemia by fluorescence in situ hibridization. Comparison with conventional cytogenetics and implications for minimal residual disease detection Hum Pathol 1997 28: 154–159

    Article  PubMed  Google Scholar 

  40. Tabernero MD, San Miguel JF, García-Sanz R, Najera ML, García-Isidoro M, Pérez-Simón JA, González M, Wiegant J, Raap A, Orfao A . Incidence of chromosome numerical changes in multiple myeloma. Fluorescence in situ hybridization analysis using 15 chromosome-specific probes Am J Pathol 1996 149: 153–161

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Cobaleda C, Gutiérrez-Cianca N, Pérez-Lozada J, Flores T, García-Sanz R, González M, Sánchez-García I . A primitive hematopoietic cell is the target for the leukemic transformation in human Philadelphia-positive acute lymphoblastic leukemia Blood 2000 95: 1007–1013

    CAS  PubMed  Google Scholar 

  42. Sánchez-García I . Consequences of chromosomal abnormalities in tumour development Ann Rev Genet 1997 31: 429–453

    Article  PubMed  Google Scholar 

  43. Sánchez-García I, Grütz G . The tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL-2 Proc Natl Acad Sci USA 1995 92: 5287–5291

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lugo YG, Pendergast AM, Muller AJ, Witte ON . Tyrosine kinase activity and transformation potential of bcr-abl oncogene products Science 1990 247: 9312–9316

    Article  Google Scholar 

  45. Verfaille CM . Chronic myelogenous leukemia: too much or too little growth, or both? Leukemia 1998 12: 136–138

    Article  Google Scholar 

  46. Skorski T, Kanakaraj P, Nieborowska-Skorska M, Ratajczak MZ, Wen SC, Zon G, Gewirtz AM, Perussia B, Calabretta B . Phosphatidylinositol – 3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells Blood 1995 86: 726–736

    CAS  PubMed  Google Scholar 

  47. Jain SK, Keeler S, Carlesso N, Druker B, Varticovski L . PI 3-kinase activation in BCR/abl transformed hematopoietic cells does not require interaction of p85 SH2 domains with p210 BCR/abl Blood 1996 88: 1542–1550

    CAS  PubMed  Google Scholar 

  48. Schlieben S, Borkhardt A, Reinisch I, Ritterbach J, Jansen JWG, Ratei R, Schrappe M, Repp R, Zimmermann M, Kabisch H, Janka-Schaub G, Bartram CR, Ludwing W-D, Riehm H, Lampert F, Harbott J . Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukaemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05–92 Leukemia 1996 10: 957–963

    CAS  PubMed  Google Scholar 

  49. Paietta E, Racevskis J, Neuberg D, Rowe JM, Goldstone AH, Wiernik PH . Expression of CD25 (interleukin-2 receptor alfa chain) in adult acute lymphoblastic leukaemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993 Leukemia 1997 11: 1887–1890

    Article  CAS  PubMed  Google Scholar 

  50. Mori T, Suzuki T, Okazaki T, Manabe A, Hosoya R, Mizutani S, Kinoshita A, Nakazawa S . A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukaemia cells with high sensitivity Leukemia 1995 9: 1233–1239

    CAS  PubMed  Google Scholar 

  51. Baruchel A, Cayuela JM, Ballerini P, Landman-Paker J, Cezard V, Haddad E, Auclerc MF, Valensi F, Cayre YE, Mancintyre EA, Sigauz F . The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts Br J Haematol 1997 99: 101–106

    Article  CAS  PubMed  Google Scholar 

  52. Hrusak O, Trka J, Zuna J, Houskova J, Bartunkova J, Stary J . Aberrant expression of KOR-SA3544 antigen in childhood acute lymphoblastic leukaemia predicts TEL-AML1 negativity Leukemia 1998 12: 1064–1070

    Article  CAS  PubMed  Google Scholar 

  53. Drexler HG, Thiel E, Ludwig WD . Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia Leukemia 1991 5: 637–645

    CAS  PubMed  Google Scholar 

  54. Lucio P, Parreira A, van den Beemd MW, van Lochem EG, van Wering ER, Baars E, Porwit-MacDonald A, Bjorklund E, Gaipa G, Biondi A, Orfao A, Janossy G, van Dongen JJ, San Miguel JF . Flow cytometry analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL Leukemia 1999 13: 419–427

    Article  CAS  PubMed  Google Scholar 

  55. Orfao A, Chillón MC, Bortoluci AM, López-Berges MC, García-Sanz R, González M, Tabernero MD, García-Marcos MA, Rasillo AI, Hernández-Rivas J, San Miguel JF . The flow cytometric pattern of CD34, CD15 and CD13 expression in acute myeloblastic leukaemia is highly characteristic of the presence of PML-Rarα gene rearrangements Haematologica 1999 84: 405–412

    CAS  PubMed  Google Scholar 

  56. Novelli EM, Ramírez M, Civin CL . Biology of CD34+/CD38− cells in lymphohematopoiesis Leuk Lymphoma 1998 31: 285–293

    Article  CAS  PubMed  Google Scholar 

  57. Terstappen LW, Huang S, Safford M, Lansdorp PM, Loken MR . Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38− progenitor cells Blood 1991 77: 1218–1227

    CAS  PubMed  Google Scholar 

  58. Loken MR, Shah VO, Dattilio KL, Civin CL . Flow cytometric analysis of human bone marrow. II Normal B lymphocyte-development Blood 1987 70: 1316–1324

    CAS  PubMed  Google Scholar 

  59. Waller EK, Olweus J, Lund-Johansen F, Huang S, Nguyen M, Guo GR, Terstappen L . The ‘common stem cell’ hypothesis reevaluated: human fetal bone marrow contains separate populations of hematopoietic and stromal progenitors Blood 1995 85: 2422–2435

    CAS  PubMed  Google Scholar 

  60. Salles G, Rodewald HR, Chin BS, Reinherz EL, Shipp MA . Inhibition of CD10/neutral endopeptidase 24.11 promotes B-cell reconstitution and maturation in vivo Proc Natl Acad Sci USA 1993 90: 7618–7622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was partially supported by a grant from the Agencia Española de Cooperaciónal (AECI) from the Ministerio de Asuntos Exteriores (Madrid, Spain). AM Bortoluci was supported by a grant from the Instituto Iberoamericano de Cooperación Internacional (Madrid, Spain).

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  1. Departamento de Medicina, Servicio General de Citometría, and Centro de Investigaciones del Cancer, University of Salamanca, Salamanca, Spain

    MD Tabernero, AM Bortoluci, A Rasillo, M García, JM Sayagués & A Orfao

  2. Servicio de Hematología, Hospital Universitario, Salamanca, Spain

    I Alaejos, MC López-Berges, R García-Sanz, M González, G Mateo & JF San Miguel

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  1. MD Tabernero
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Tabernero, M., Bortoluci, A., Alaejos, I. et al. Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expression. Leukemia 15, 406–414 (2001). https://doi.org/10.1038/sj.leu.2402060

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