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Characterization of aberrant phenotypes in acute myeloblastic leukemia

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Abstract

The existence of leukemic-associated phenotypes has been suggested to be a valuable tool for the detection of minimal residual disease (MRD) in AML patients, as they would allow to distinguish leukemic blast cells from normal hematopoietic progenitors. The present study was designed to analyze in which proportion of AML patients the immunological detection of MRD is feasible, based on the presence of aberrant phenotypes that allow the distinction of leukemic from normal cells. For this purpose we have prospectively investigated the blast cells from 40 AML patients at diagnosis with a large panel of MoAb in double and triple staining combinations analyzed at flow cytometry, in order to detect aberrant phenotypes on blast cells (lineage infidelity, antigenic overexpression, and asynchronous antigenic expression, as well as aberrant lightscatter pattern). In the analysis of the 40 AML cases more than one blast cell subset, distinguished by its different antigenic expression, was detected in 85% of the patients: five different phenotypic blast cell subsets were observed in six cases, four in 13 patients, three subsets in three cases, and two in 12 patients; only six cases showed a homogeneous phenotypical blast cell population. Twenty-nine of the 40 AML cases analyzed (73%) showed the existence of at least one aberrant phenotype: in 15 cases the myeloid blast cells co-expressed lymphoid-associated antigens (CD2, CD5, CD7, and/or CD19) - lineage infidelity -; asynchronous antigen expression was detected in 25 patients (CD34+CD56+, CD34+CD11b+, CD34+CD14+, CD117+CD15+, CD33-CD13+, CD13-CD15+, HLADR+CD15+++, HLADR-CD14+CD11b+ CD4+); seven cases displayed antigen overexpression (CD13, CD33, CD15, or CD14); and in 13 patients leukemic cells had an abnormal FSC/SSC distribution according to their phenotype. These results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients.

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References

  1. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of acute leukemias. A report of the French-American-British Cooperative Group. Br J Haematol 33:451–458

    PubMed  Google Scholar 

  2. Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick H, Sultan C(FAB group) (1985) Proposed revised criteria for the classification of AML. Ann Intern Med 103:626–629

    PubMed  Google Scholar 

  3. Biondi A, Rambaldi A, Alcalay M, Pandolfi PP, LoCoco F, Diverio D, Rossi V, Mencarelli A, Longo L, Zangrilli D, Masera G, Barbui T, Mandelli F, Grignani F, Pelicci PG (1991) Rar-alfa gene rearrangements as genetic marker for diagnosis and monitoring in acute promyelocytic leukemia. Blood 77:1418–1422

    PubMed  Google Scholar 

  4. Biondi A, Rambaldi A, Pandolfi PP, Rossi V, Giudici G, Alcalay M, Lo Coco F, Diverio D, Pogliani EM, Lanzi EM, Mandelli F, Masera G, Barbui T, Pelicci G (1992) Molecular monitoring of the myl/Retinoic acid receptor-alfa fusion gene in acute promyelocytic leukemia by polymerase chain reaction. Blood 80:492–497

    PubMed  Google Scholar 

  5. Bradstock KF, Kirk J, Grimsley PG, Kabral A, Hughes WG (1989) Unusual immunophenotypes in acute leukaemias: incidence and clinical correlations. Br J Haematol 72:512–518

    PubMed  Google Scholar 

  6. Campana D (1994) Applications of cytometry to study acute leukemia: in vitro determination of drug sensitivity and detection of minimal residual disease. Cytometry 18:68–74

    PubMed  Google Scholar 

  7. Campana D, Coustan-Smith E, Janossy G (1990) The immunologic detection of minimal residual disease in acute leukemia. Blood 76:163–171

    PubMed  Google Scholar 

  8. Campana D, Coustan-Smith E, Behm FG (1991) The definition of remission in acute leukemia with immunologic techniques. Bone Marrow Transplant 8:429–437

    PubMed  Google Scholar 

  9. Coustan-Smith E, Behm FG, Hurwitz CA, Rivera GK, Campana D (1993) N-Cam (CD56) expression by CD34+ malignant myeloblasts has implications for minimal residual disease detection in acute myeloid leukemia. Leukemia 7:853–858

    PubMed  Google Scholar 

  10. De Thé H, Chomienne C, Lanotte M, Degos L, Dejean A (1990) The t (15;17) of acute promyelocytic leukaemia fuses the retinoic acid receptor alfa gene to a novel transcribed locus. Nature 347:558–561

    PubMed  Google Scholar 

  11. Del Vecchio L, Finizio O, Pardo C, Pane N, Schiavone EM, Vacca C, Ferrara F (1991) Coordinate expression of T-cell antigens on acute myelogenous leukemia and of myeloid antigens on T-acute lymphoblastic leukemia. Speculation on a highly balanced bilinearity. Leukemia 5:815–818

    PubMed  Google Scholar 

  12. Drach J, Gattringer C, Huber H (1991) Combined flow cytometric assessment of cell surface antigens and nuclear TdT for the detection of minimal residual disease in acute leukaemia. Br J Haematol 77:37–42

    PubMed  Google Scholar 

  13. Drach J, Drach D, Glassl H, Gattringer C, Huber H (1992) Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease. Cytometry 13:893–901

    PubMed  Google Scholar 

  14. Drexler HG, Sperling C, Ludwing WD (1993) Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia. Leukemia 7:1142–1150

    PubMed  Google Scholar 

  15. Drexler HG, Thield E, Ludwing WD (1993) Acute myeloid leukemias expressing lymphoid-associated antigens: diagnostic incidence and prognostic significance. Leukemia 7:489–498

    PubMed  Google Scholar 

  16. Gerhartz HH, Schmetzer H (1990) Detection of minimal residual disease in acute myeloid leukemia. Leukemia 4:508–512

    PubMed  Google Scholar 

  17. Macedo A (1994) Estudio antigénico de la hematopoyesis normal y sus implicaciones en la detection de enfermedad mínima residual en leucemias agudas mieloblásticas. PhD thesis, Universidad de Salamanca

  18. Macedo A, Orfão A, Martinez M, Vidriales MB, Valverde B, Lopez-Berges MC, San Miguel JF (1995) Immunophenotype of CD117 cells in human bone marrow. Implications for the detection of minimal residual disease in AML. Br J Haematol (in press)

  19. Macedo A, Orfão A, Gonzalez M, Vidriales MB, Lopez Berges MC, Martínez A, San Miguel JF (1995) Immunological detection of blast cell subpopulations in acute myeloblastic leukemia at diagnosis: implications for minimal residual disease studies. Leukemia (in press)

  20. Orfão A, Ciudad J, Lopez-Berges MC, Lopez A, Vidriales B, Caballero MD, Valverde B, Gonzalez M, San Miguel JF (1994) Acute lymphoblastic leukemia (ALL): Detection of minimal residual disease (MRD) at flow cytometry. Leuk Lymph 13 [Suppl 1]:87–90

    Google Scholar 

  21. Reading CL, Estey EH, Huh YO, Claxton DF, Sánchez G, Terstappen LWMM, O'Brien MC, Baron S, Deisseroth AB (1993) Expression of unusual immunophenotype combinations in acute myelogenous leukemia. Blood 81:3083–3090

    PubMed  Google Scholar 

  22. Terstappen LWMM, Mickaels RA, Dost R, Loken MR (1990) Increased light scattering resolution facilitates multidimensional flow cytometric analysis. Cytometry 11:506–512

    PubMed  Google Scholar 

  23. Terstappen LWMM, Safford M, Konemann S, Loken MR, Zurlutter K, Büchner T, Hiddemann W, Wörmann B (1991) Flow cytometric characterization of acute myeloid leukemia. II. Phenotypic heterogeneity at diagnosis. Leukemia 5:757–767

    Google Scholar 

  24. Wörman B, Griesinger F, Innig G, Kolkmeyer A, Toepken S, Grove D, Büchner T, Hiddemann W, Terstappen WMM (1992) Detection of residual leukemic cells in patients with acute myeloid leukemia based on cell surface antigen expression. Sangre 37:133–135

    PubMed  Google Scholar 

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Macedo, A., Orfão, A., Vidriales, M.B. et al. Characterization of aberrant phenotypes in acute myeloblastic leukemia. Ann Hematol 70, 189–194 (1995). https://doi.org/10.1007/BF01700374

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