Clinical, Molecular, and Prognostic Significance of WHO Type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and Various Other 3q Abnormalities in Acute Myeloid Leukemia

Sanne Lugthart, S Groschel, Berna Beverloo, S Kayser, Peter Valk, SL Van Zelderen-Bhola, GJ Ossenkoppele, E Vellenga, E de Ruiter, U Schanz, G Verhoef, P Vandenberghe, A Ferrant, CH Koohne, M Pfreundschuh, HA Horst, E Koller, M von Lilienfeld-Toal, M Bentz, A GanserB Schlegelberger, M Jotterand, J Krauter, T Pabst, M Theobald, RF Schlenk, Ruud Delwel, K Doohner, Bob Löwenberg, H Dohner

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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 HematoOncology 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.
Original languageUndefined/Unknown
Pages (from-to)3890-3898
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number24
Publication statusPublished - 2010

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