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Title: 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
Authors: Lugthart, Sanne ×
Gröschel, Stefan
Beverloo, H Berna
Kayser, Sabine
Valk, Peter J M
van Zelderen-Bhola, Shama Lydia
Ossenkoppele, Gert Jan
Vellenga, Edo
van den Berg-de Ruiter, Eva
Schanz, Urs
Verhoef, Gregor
Vandenberghe, Peter
Ferrant, Augustin
Köhne, Claus-Henning
Pfreundschuh, Michael
Horst, Heinz A
Koller, Elisabeth
von Lilienfeld-Toal, Marie
Bentz, Martin
Ganser, Arnold
Schlegelberger, Brigitte
Jotterand, Martine
Krauter, Jürgen
Pabst, Thomas
Theobald, Matthias
Schlenk, Richard F
Delwel, Ruud
Döhner, Konstanze
Löwenberg, Bob
Döhner, Hartmut #
Issue Date: Aug-2010
Publisher: Grune & Stratton
Series Title: Journal of Clinical Oncology vol:28 issue:24 pages:3890-3898
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.
URI: 
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hematology Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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