Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan.

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.

[1]  H. Koeffler Syndromes of acute nonlymphocytic leukemia. , 1987, Annals of internal medicine.

[2]  C. Bloomfield,et al.  Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia , 1994 .

[3]  Y. C. Chen,et al.  Cytogenetic studies, ras mutation, and clinical characteristics in primary myelodysplastic syndrome. A study on 68 Chinese patients in Taiwan. , 1994, Cancer genetics and cytogenetics.

[4]  C. Bloomfield,et al.  The clinical significance of karyotype in acute myelogenous leukemia. , 1989, Cancer genetics and cytogenetics.

[5]  C. Ross,et al.  Acute biphenotypic leukaemia: immunophenotypic and cytogenetic analysis , 1993, British journal of haematology.

[6]  J. Radich,et al.  N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. , 1990, Blood.

[7]  K. Ohyashiki,et al.  TRISOMY 11 IN NONLYMPHOCYTIC NEOPLASIA , 1988, British journal of haematology.

[8]  F. Sigaux,et al.  Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias. , 1987, Cancer genetics and cytogenetics.

[9]  Y. C. Chen,et al.  Comparison of clinical and biologic features between myeloid and lymphoid transformation of Philadelphia chromosome positive chronic myeloid leukemia. , 1993, Cancer genetics and cytogenetics.

[10]  G Flandrin,et al.  Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[11]  C. Bloomfield,et al.  Use of surface marker analysis to predict outcome of adult acute myeloblastic leukemia. , 1986, Blood.

[12]  Correlation of cytogenetic patterns and clinicobiological features in adult acute myeloid leukemia expressing lymphoid markers. , 1992 .

[13]  V. Mitchell,et al.  Transmission of hepatitis B by dry heat treated factor VIII and IX concentrates. , 1988, British journal of haematology.

[14]  Y. Kaneko,et al.  Trisomy 11 in chronic myelomonocytic leukemia: report of two cases and review of the literature. , 1988, Cancer genetics and cytogenetics.

[15]  F. Behm,et al.  14q32 translocations are associated with mixed-lineage expression in childhood acute leukemia. , 1990, Blood.

[16]  J. Rowley,et al.  Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. , 1984, The American journal of medicine.

[17]  D. Campana,et al.  Rearrangement of immunoglobulin and T cell antigen receptor genes in acute myeloid leukemia with lymphoid-associated markers. , 1987, Leukemia.

[18]  R. Beuscart,et al.  Cytogenetics and their prognostic value in de novo acute myeloid leukaemia: a report on 283 cases , 1989, British journal of haematology.

[19]  F. Mitelman,et al.  Clustering of aberrations to specific chromosomes in human neoplasms. IV. A survey of 1,871 cases. , 2009, Hereditas.

[20]  F. Solé,et al.  Cytogenetic studies in acute nonlymphocytic leukemia. , 1992, Cancer genetics and cytogenetics.

[21]  A. Rimm,et al.  Basic biostatistics in medicine and epidemiology , 1980 .

[22]  J. L. Bos,et al.  Mutations in N-ras predominate in acute myeloid leukemia. , 1987, Blood.

[23]  Yao-chang Chen,et al.  Chromosome studies on 30 Chinese patients with acute nonlymphocytic leukemia in Taiwan. , 1988, Cancer genetics and cytogenetics.

[24]  B. Johansson,et al.  Geographic heterogeneity of neoplasia‐associated chromosome aberrations , 1991, Genes, chromosomes & cancer.

[25]  D. Catovsky,et al.  Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[26]  C. Marosi,et al.  Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  F. Sigaux,et al.  Prognostic significance of chromosomal abnormalities in acute nonlymphocytic leukemia: a study of 343 patients. , 1987, Cancer genetics and cytogenetics.

[28]  L. Stuppia,et al.  Cytogenetic survey of 80 patients with acute nonlymphocytic leukemia. , 1992, Cancer genetics and cytogenetics.

[29]  C. Marosi,et al.  Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML. , 1992, Cancer genetics and cytogenetics.

[30]  Edward J. Lee,et al.  Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia. , 1989, Blood.

[31]  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.

[32]  J. Griffin,et al.  Prognostic value of lymphocyte surface markers in acute myeloid leukemia. , 1991, Blood.

[33]  D. Treille,et al.  Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy , 1989, British journal of haematology.

[34]  F. Mitelman Geographic heterogeneity of chromosome aberrations in hematologic disorders. , 1986, Cancer genetics and cytogenetics.

[35]  Natalie W. Paul,et al.  Birth defects, original article series , 1982 .

[36]  Y. C. Chen,et al.  Characterization of acute myeloid leukemia (AML) coexpressing lymphoid markers: different biologic features between T-cell antigen positive and B-cell antigen positive AML. , 1993, Leukemia.

[37]  Liu Et The role of ras gene mutations in myeloproliferative disorders. , 1990 .

[38]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[39]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[40]  J. Matthews,et al.  Prognostic value of immunophenotyping in acute myeloid leukemia. Australian Leukaemia Study Group. , 1994, Blood.

[41]  H. Gralnick,et al.  Proposals for the Classification of the Acute Leukaemias French‐American‐British (FAB) Co‐operative Group , 1976, British journal of haematology.

[42]  M. Pike,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. , 1977, British Journal of Cancer.

[43]  H. Griesser,et al.  Gene rearrangements and translocations in lymphoproliferative diseases , 1989 .

[44]  Iscn International System for Human Cytogenetic Nomenclature , 1978 .

[45]  M. Bar‐eli,et al.  The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing. , 1990, Blood.

[46]  J. Reuben,et al.  Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia. , 1988, Blood.