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.

Details

Serval ID
serval:BIB_906C954AD411
Type
Article: article from journal or magazin.
Collection
Publications
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.
Journal
Journal of Clinical Oncology
Author(s)
Lugthart S., Gröschel S., Beverloo H.B., Kayser S., Valk P.J., van Zelderen-Bhola S.L., Jan Ossenkoppele G., Vellenga E., van den Berg-de Ruiter E., Schanz U., Verhoef G., Vandenberghe P., Ferrant A., Köhne C.H., Pfreundschuh M., Horst H.A., Koller E., von Lilienfeld-Toal M., Bentz M., Ganser A., Schlegelberger B., Jotterand M., Krauter J., Pabst T., Theobald M., Schlenk R.F., Delwel R., Döhner K., Löwenberg B., Döhner H.
ISSN
1527-7755[electronic], 0732-183X[linking]
Publication state
Published
Issued date
2010
Volume
28
Number
24
Pages
3890-3898
Language
english
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.
Keywords
Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Cell Adhesion Molecules/metabolism, Chromosome Aberrations, Chromosome Inversion, Chromosomes, Human, Pair 3, Clinical Trials as Topic, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Genes, ras, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meiers Estimate, Karyotyping, Leukemia, Myeloid, Acute/genetics, Leukemia, Myeloid, Acute/metabolism, Male, Middle Aged, Monosomy, Multivariate Analysis, Mutation, Neoplasm Proteins/metabolism, Odds Ratio, Predictive Value of Tests, Prognosis, Remission Induction, Translocation, Genetic, Treatment Outcome, Tumor Markers, Biological/metabolism
Pubmed
Web of science
Create date
08/09/2010 16:21
Last modification date
03/03/2018 19:25
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