Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Oncology, BONE-MARROW-TRANSPLANTATION, ACUTE MYELOGENOUS LEUKEMIAS, COLONY-STIMULATING FACTOR, ADULT PATIENTS, CYTOGENETIC ABNORMALITIES, POSTREMISSION THERAPY, NORMAL-TISSUES, EXPRESSION, DIAGNOSIS, CANCER, Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Cell Adhesion Molecules, Chromosome Aberrations, Chromosome Inversion, Chromosomes, Human, Pair 3, Clinical Trials as Topic, DNA-Binding Proteins, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Genes, ras, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Karyotyping, Leukemia, Myeloid, Acute, MDS1 and EVI1 Complex Locus Protein, Male, Middle Aged, Monosomy, Multivariate Analysis, Mutation, Neoplasm Proteins, Odds Ratio, Predictive Value of Tests, Prognosis, Proto-Oncogenes, Remission Induction, Transcription Factors, Translocation, Genetic, Treatment Outcome, 1103 Clinical Sciences, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis

Abstract:

PURPOSE Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) [inv(3)/t(3;3)] is recognized as a distinctive entity in the WHO classification. Risk assignment and clinical and genetic characterization of AML with chromosome 3q abnormalities other than inv(3)/t(3;3) remain largely unresolved. PATIENTS AND METHODS Cytogenetics, molecular genetics, therapy response, and outcome analysis were performed in 6,515 newly diagnosed adult AML patients. Patients were treated on Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research (HOVON/SAKK; n = 3,501) and German-Austrian Acute Myeloid Leukemia Study Group (AMLSG; n = 3,014) protocols. EVI1 and MDS1/EVI1 expression was determined by real-time quantitative polymerase chain reaction. Results 3q abnormalities were detected in 4.4% of AML patients (288 of 6,515). Four distinct groups were defined: A: inv(3)/t(3;3), 32%; B: balanced t(3q26), 18%; C: balanced t(3q21), 7%; and D: other 3q abnormalities, 43%. Monosomy 7 was the most common additional aberration in groups (A), 66%; (B), 31%; and (D), 37%. N-RAS mutations and dissociate EVI1 versus MDS1/EVI1 overexpression were associated with inv(3)/t(3;3). Patients with inv(3)/t(3;3) and balanced t(3q21) at diagnosis presented with higher WBC and platelet counts. In multivariable analysis, only inv(3)/t(3;3), but not t(3q26) and t(3q21), predicted reduced relapse-free survival (hazard ratio [HR], 1.99; P < / .001) and overall survival (HR, 1.4; P = .006). This adverse prognostic impact of inv(3)/t(3;3) was enhanced by additional monosomy 7. Group D 3q aberrant AML also had a poor outcome related to the coexistence of complex and/or monosomal karyotypes and cryptic inv(3)/t(3;3). CONCLUSION Various categories of 3q abnormalities in AML can be distinguished according to their clinical, hematologic, and genetic features. AML with inv(3)/t(3;3) represents a distinctive subgroup with unfavorable prognosis.