Impact of immunophenotyping on management of acute leukemias.

BACKGROUND AND OBJECTIVE The diagnosis of acute leukemias (AL) requires a multiparametric approach in order to apply risk-adapted therapeutic protocols and appreciate the potential outcome of any given patient. Blast cells immunophenotyping is a key test in this issue, yet the information provided by immunophenotyping has become staggering, and it may be difficult to identify relevant characteristics clearly. This manuscript provides a critical review of the literature regarding the importance of immunophenotyping in acute leukemia diagnosis and management. DATA SOURCES AND METHODS The information given here is based on the experience of the authors, on their literature files and on additional material retrieved through articles and reviews covered by the Institute for Scientific Information (ISI) and the Medline database. Studies with proper definition of the patients and sufficient information regarding follow-up were considered. RESULTS Immunophenotyping allows an early confirmation of AL diagnosis and establishes lineage assignment. Adequate and comprehensive panels of monoclonal antibodies also allow detection of aberrant immunophenotypic profiles of prognostic value or of use in detecting minimal residual disease. A number of unusual immunophenotypic features are also associated with prognosis. The development of new antibodies, new insights in the functional properties of differentiation antigens, and the quantimetric approach of immunophenotyping will keep this field changing. Moreover, as therapeutic protocols evolve, some earlier results need to be reconsidered. INTERPRETATION AND CONCLUSIONS Immunophenotyping, together with cytologic, karyotypic and molecular approaches, retains a crucial place in the diagnosis and management of acute leukemias. It remains a rather specialized approach and should be interpreted in a multidisciplinary perspective, considering for each patient the idiosyncrasies possibly relevant to prognosis.

[1]  A. Órfão,et al.  Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL , 1999, Leukemia.

[2]  R. Scheper,et al.  Overexpression of lung‐resistance protein and increased P‐glycoprotein function in acute myeloid leukaemia cells predict a poor response to chemotherapy and reduced patient survival , 1998, British journal of haematology.

[3]  J. Downing,et al.  Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  F. Mandelli,et al.  Acute promyelocytic leukemia: a curable disease , 1998, Leukemia.

[5]  A Orfao,et al.  Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  M. Borowitz,et al.  Surface antigen phenotype can predict TEL-AML1 rearrangement in childhood B-precursor ALL: a Pediatric Oncology Group study , 1998, Leukemia.

[7]  J W Gratama,et al.  Performance of calibration standards for antigen quantitation with flow cytometry. , 1998, Cytometry.

[8]  E. Thiel,et al.  Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89. , 1998, Blood.

[9]  J. Harbott,et al.  Immunophenotype and clinical characteristics of CD45-negative and CD45-positive childhood acute lymphoblastic leukemia , 1998, Annals of Hematology.

[10]  R. Consolini,et al.  Expression of myeloid markers lacks prognostic impact in children treated for acute lymphoblastic leukemia: Italian experience in AIEOP-ALL 88-91 studies. , 1998, Blood.

[11]  G. Pratt,et al.  Modern molecular diagnostics and the management of haematological malignancies. , 1998, Clinical and laboratory haematology.

[12]  H. Kluin-Nelemans,et al.  A strong expression of CD44-6v correlates with shorter survival of patients with acute myeloid leukemia. , 1998, Blood.

[13]  J. Hess,et al.  Guidelines for the diagnosis of leukemia or lymphoma in children. , 1998, American journal of clinical pathology.

[14]  D. Catovsky,et al.  Detection of minimal residual disease in B‐lineage acute lymphoblastic leukaemia by quantitative flow cytometry , 1998, British journal of haematology.

[15]  R. Pieters,et al.  Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. , 1998, Blood.

[16]  Elaine Coustan-Smith,et al.  Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia , 1998, The Lancet.

[17]  N. Heerema,et al.  Biology and treatment of childhood T-lineage acute lymphoblastic leukemia. , 1998, Blood.

[18]  J. Bennett,et al.  Acute myeloid leukaemia expressing the leucocyte integrin CD11b — a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis , 1998 .

[19]  M. Baer Assessment of minimal residual disease in patients with acute leukemia , 1998, Current opinion in oncology.

[20]  P. Boquet,et al.  Functional analysis of four tetraspans, CD9, CD53, CD81, and CD82, suggests a common role in costimulation, cell adhesion, and migration: only CD9 upregulates HB-EGF activity. , 1997, Cellular immunology.

[21]  S. Tura,et al.  High bcl-2 expression in acute myeloid leukemia cells correlates with CD34 positivity and complete remission rate , 1997, Leukemia.

[22]  A T Look,et al.  Oncogenic transcription factors in the human acute leukemias. , 1997, Science.

[23]  L. Degos Differentiation therapy in acute promyelocytic leukemia: European experience , 1997, Journal of cellular physiology.

[24]  F. Behm,et al.  U.S.-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: selection of antibody combinations. , 1997, Cytometry.

[25]  G. Sanchez-Williams,et al.  Minimal residual disease in acute myelogenous leukaemia and myelodysplastic syndromes: a follow‐up of patients in clinical remission , 1997, British journal of haematology.

[26]  J. Robert,et al.  Measuring multidrug resistance expression in human malignancies: elaboration of consensus recommendations. , 1997, Seminars in hematology.

[27]  F. Sigaux,et al.  The majority of myeloid‐antigen‐positive (My+) childhood B‐cell precursor acute lymphoblastic leukaemias express TEL‐AML1 fusion transcripts , 1997, British journal of haematology.

[28]  Marcos González,et al.  Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients , 1997 .

[29]  J. Miguel,et al.  Functional expression of MDR-1 in acute myeloid leukemia: correlation with the clinical-biological, immunophenotypical, and prognostic disease characteristics , 1997, Annals of Hematology.

[30]  C. Bloomfield,et al.  Expression of the neural cell adhesion molecule CD56 is associated with short remission duration and survival in acute myeloid leukemia with t(8;21)(q22;q22). , 1997, Blood.

[31]  M. Volm,et al.  Expression of lung resistance-related protein (LRP) in initial and relapsed childhood acute lymphoblastic leukemia , 1997, Anti-cancer drugs.

[32]  M. Spitaler,et al.  Multidrug resistance in acute leukemia: a comparison of different diagnostic methods , 1997, Leukemia.

[33]  S. Tura,et al.  Incidence and prognostic relevance of CD34 expression in acute myeloblastic leukemia: analysis of 141 cases. , 1997, Leukemia research.

[34]  F. Lanza,et al.  Comparative analysis of different permeabilization methods for the flow cytometry measurement of cytoplasmic myeloperoxidase and lysozyme in normal and leukemic cells. , 1997, Cytometry.

[35]  S. Bigner,et al.  Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes. , 1997, American journal of clinical pathology.

[36]  A. Look,et al.  Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study. , 1997, Blood.

[37]  W. Ludwig,et al.  Expression of intercellular adhesion molecule 1 (ICAM‐1) in childhood acute lymphoblastic leukaemia: correlation with clinical features and outcome , 1997, British journal of haematology.

[38]  J. Gratama,et al.  Pitfalls in the immunophenotyping of leukaemia and leukaemic lymphomas: survey of 9 years of quality control in The Netherlands , 1996, British journal of haematology.

[39]  M. Zöller,et al.  Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression. , 1996, Leukemia research.

[40]  G. Gaudernack,et al.  Differences in the distribution of CD34 epitopes on normal haemopoietic progenitor cells and leukaemic blast cells , 1996, British journal of haematology.

[41]  J. V. van Dongen,et al.  Flow cytometric detection of intracellular antigens for immunophenotyping of normal and malignant leukocytes. , 1996, Leukemia.

[42]  W. Wilmanns,et al.  Association of bcl-2, bax, bcl-xL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia. , 1996, Leukemia.

[43]  Costan,et al.  Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. , 1996, Cancer research.

[44]  A. Morley,et al.  Relationship between minimal residual disease and outcome in adult acute lymphoblastic leukemia. , 1996, Blood.

[45]  B. Löwenberg Treatment of the elderly patient with acute myeloid leukaemia. , 1996, Bailliere's clinical haematology.

[46]  M. Béné,et al.  Expression and long-term prognostic value of CD34 in childhood and adult acute lymphoblastic leukemia. , 1995, Leukemia & lymphoma.

[47]  E. Wattel,et al.  Expression of the multidrug resistance P glycoprotein in newly diagnosed adult acute lymphoblastic leukemia: absence of correlation with response to treatment. , 1995, Leukemia.

[48]  X. Thomas,et al.  Expression of N-CAM (CD56) on acute leukemia cells: relationship with disease characteristics and outcome. , 1995, Leukemia & lymphoma.

[49]  F. Lanza,et al.  Photomultiplier voltage setting: possible important source of variability in molecular equivalents of soluble fluorochrome (MESF) calculation? , 1995, Cytometry.

[50]  M. Minden,et al.  Acute leukemia in adults , 1995, Current opinion in hematology.

[51]  J. Harbott,et al.  Clinical, morphologic, cytogenetic and prognostic implications of CD34 expression in childhood and adult de novo AML. , 1995, Leukemia & lymphoma.

[52]  A. Órfão,et al.  Prognostic value of S‐phase cells in AML patients , 1995, British journal of haematology.

[53]  C. Ludescher,et al.  Low frequency of activity of P-glycoprotein (P-170) in acute lymphoblastic leukemia compared to acute myeloid leukemia. , 1995, Leukemia.

[54]  F. Sigaux,et al.  Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: an analysis of a prospective trial including 562 tested patients (LALA87). French Group on Therapy for Adult Acute Lymphoblastic Leukemia. , 1994, Blood.

[55]  M. Grever,et al.  HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3. , 1994, Blood.

[56]  R. Pirker,et al.  P-glycoprotein expression as unfavorable prognostic factor in acute myeloid leukemia. , 1994, Leukemia.

[57]  A. Órfão,et al.  Expression of NK and lymphoid-associated antigens in blast cells of acute myeloblastic leukemia. , 1993, Leukemia.

[58]  M. Borowitz,et al.  Immunophenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis. , 1993, American journal of clinical pathology.

[59]  F. Behm,et al.  Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia. , 1993, Blood.

[60]  O. Fardel,et al.  Expression of the multidrug resistance-associated P-glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications. , 1993, Blood.

[61]  S. Korsmeyer,et al.  Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. , 1993, Blood.

[62]  E. Thiel,et al.  Acute myeloid leukemias expressing lymphoid-associated antigens: diagnostic incidence and prognostic significance. , 1993, Leukemia.

[63]  V. Praloran,et al.  Characteristics of pro-T ALL subgroups: comparison with late T-ALL. The Groupe d'Etude Immunologique des Leucémies. , 1993, Leukemia.

[64]  F Lampert,et al.  Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group. , 1992, Blood.

[65]  M. Béné,et al.  Multiphenotypic acute leukemias: clinicopathologic correlations and response to therapy. , 1992, Leukemia & lymphoma.

[66]  F. Mandelli,et al.  ACUTE PROMYELOCYTIC LEUKAEMIA , 1992, British journal of haematology.

[67]  E. Solary,et al.  Surface markers in adult acute myeloblastic leukemia: correlation of CD19+, CD34+ and CD14+/DR--phenotypes with shorter survival. Groupe d'Etude Immunologique des Leucémies (GEIL). , 1992, Leukemia.

[68]  J. Magaud,et al.  Expression of surface adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3) in adult acute leukemia: relationship with initial characteristics and prognosis. , 1992, Leukemia.

[69]  F. Behm,et al.  Lack of CD45 antigen on blast cells in childhood acute lymphoblastic leukemia is associated with chromosomal hyperdiploidy and other favorable prognostic features , 1992 .

[70]  T. Tsuruo,et al.  Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. , 1992, Blood.

[71]  K. Weinberg,et al.  Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood. , 1991, The New England journal of medicine.

[72]  A. Look,et al.  Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  F. Davey,et al.  The use of cytochemical procedures in the diagnosis and management of acute and chronic myeloid leukemia. , 1990, Clinics in laboratory medicine.

[74]  M. Borowitz,et al.  Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study. , 1989, Blood.

[75]  E. Berg,et al.  Homing Receptors and Vascular Addressins: Cell Adhesion Molecules that Direct Lymphocyte Traffic , 1989, Immunological reviews.

[76]  A. Órfão,et al.  Prognostic value of immunological markers in acute myeloblastic leukemia. , 1989, Leukemia.

[77]  K. Foon,et al.  Immunologic classification of leukemia and lymphoma. , 1986, Blood.

[78]  P. Carayon,et al.  Cytofluorometric quantification of cell-surface antigens by indirect immunofluorescence using monoclonal antibodies. , 1985, Journal of immunological methods.

[79]  M. Fackler,et al.  Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. , 1984, Journal of immunology.

[80]  Banerjea Jc ACUTE MYELOBLASTIC LEUKAEMIA. , 1963 .

[81]  飯島 也万 Functional expression of Fas (CD95) in acute myeloid leukemia cells in the context of CD34 and CD38 expression : possible correlation with sensitivity to chemotherapy , 1999 .

[82]  E. Solary,et al.  Immunophenotypic patterns and cytogenetic anomalies in acute non-lymphoblastic leukemia subtypes: a prospective study of 432 patients , 1998, Leukemia.

[83]  E. Solary,et al.  PreB1 (CD10-) acute lymphoblastic leukemia: immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children. The Groupe dEtude Immunologique des Leucémies. , 1998, Leukemia & lymphoma.

[84]  E. Koníková,et al.  Intracellular markers in acute myeloid leukemia diagnosis. , 1998, Neoplasma.

[85]  E. Thiel,et al.  Immunophenotypic and Genotypic Features , Clinical Characteristics , and Treatment Outcome of Adult ProB Acute Lymphoblastic Leukemia : Results of the German Multicenter Trials , 1998 .

[86]  M. Sanz,et al.  P-glycoprotein expression and prognostic value in acute myeloid , 1998 .

[87]  M. Karlsson,et al.  Differences in CD14 and α-naphthyl acetate esterase positivity and relation to prognosis in AML , 1998 .

[88]  F. Mandelli,et al.  Therapy of acute myeloid leukemia: towards a patient-oriented, risk-adapted approach. , 1998, Haematologica.

[89]  C. Pui,et al.  Recent advances in the biology and treatment of childhood acute lymphoblastic leukemia , 1997, Current opinion in hematology.

[90]  M. Sanz,et al.  P-glycoprotein expression and prognostic value in acute myeloid leukemia. , 1998, Haematologica.

[91]  Egil The value of c-kit in the diagnosis of biphenotypic acute leukemia , 1998, Leukemia.

[92]  A. Órfão,et al.  Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. , 1997, Blood.

[93]  P. Musto,et al.  Adult and childhood acute lymphoblastic leukemia: clinico-biological differences based on CD34 antigen expression. , 1997, Haematologica.

[94]  D. Catovsky,et al.  Definition of acute biphenotypic leukemia. , 1997, Haematologica.

[95]  D. Arthur,et al.  CD2 antigen expression on leukemic cells as a predictor of event-free survival after chemotherapy for T-lineage acute lymphoblastic leukemia: a Children's Cancer Group study. , 1996, Blood.

[96]  C. Pui,et al.  Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[97]  T. Barbui,et al.  Therapeutic impact of adult-type acute lymphoblastic leukemia regimens in B-cell/L3 acute leukemia and advanced-stage Burkitt's lymphoma. , 1996, Haematologica.

[98]  A. Pashov,et al.  Levels of CAF7 (CD98) expression correlate with the complete remission duration in childhood acute leukemia. , 1996, Leukemia research.

[99]  C. Taylor,et al.  Diagnosis and classification of the acute leukemias: recent advances and controversial issues. , 1996, Hematopathology and molecular hematology.

[100]  G. Papa,et al.  Lineage identification of acute leukemias: relevance of immunologic and ultrastructural techniques. , 1995, Hematologic pathology.

[101]  F. Lanza,et al.  CD34+ leukemic cells assessed by different CD34 monoclonal antibodies. , 1995, Leukemia & lymphoma.

[102]  L. Debusscher,et al.  Immunological definition of acute minimally differentiated myeloid leukemia (MO) and acute undifferentiated leukemia (AUL). , 1995, Leukemia & lymphoma.

[103]  A. Órfão,et al.  Acute lymphoblastic leukemia (ALL): detection of minimal residual disease (MRD) at flow cytometry. , 1994, Leukemia & lymphoma.

[104]  F. Lanza,et al.  Prognostic value of immunophenotypic characteristics of blast cells in acute myeloid leukemia. , 1994, Leukemia & lymphoma.

[105]  R. Garand,et al.  A new approach of acute lymphoblastic leukemia immunophenotypic classification: 1984-1994 the GEIL experience. Groupe d'Etude Immunologique des Leucémies. , 1994, Leukemia & lymphoma.

[106]  O. Haas,et al.  Myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. Austrian Pediatric Oncology Group. , 1993, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[107]  R. Garand,et al.  Incidence, clinical and laboratory features, and prognostic significance of immunophenotypic subgroups in acute lymphoblastic leukemia: the GEIL experience. , 1993, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[108]  O. Majdic,et al.  Flow cytometric analysis of intracellular myeloperoxidase and lactoferrin in leukemia diagnosis. , 1993, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[109]  M. Roth,et al.  Application of the polymerase chain reaction for detection of minimal residual disease of hematologic malignancies. , 1991, Henry Ford Hospital medical journal.

[110]  Roth Ms,et al.  Application of the polymerase chain reaction for detection of minimal residual disease of hematologic malignancies. , 1991 .

[111]  M. Thomas,et al.  The leukocyte common antigen family. , 1989, Annual review of immunology.

[112]  R. Coles Acute myeloblastic leukaemia. , 1972, Nursing times.

[113]  H. J. Woodliff,et al.  ACUTE PROMYELOCYTIC LEUKAEMIA. , 1964, The Medical journal of Australia.