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 LeukemiaLugthart, S., Groschel, S., Beverloo, H. B., Kayser, S., Valk, P. J. M., van Zelderen-Bhola, S. L., Ossenkoppele, G. J., Vellenga, E., van den Berg-de Ruiter, E., Schanz, U., Verhoef, G., Vandenberghe, P., Ferrant, A., Kohne, 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., Dohner, K., Lowenberg, B. & Doehner, H., 20-Aug-2010, In : Journal of Clinical Oncology. 28, 24, p. 3890-3898 9 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
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
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.
|Number of pages||9|
|Journal||Journal of Clinical Oncology|
|Publication status||Published - 20-Aug-2010|
- BONE-MARROW-TRANSPLANTATION, ACUTE MYELOGENOUS LEUKEMIAS, COLONY-STIMULATING FACTOR, CYTOGENETIC ABNORMALITIES, ADULT PATIENTS, POSTREMISSION THERAPY, ELDERLY-PATIENTS, NORMAL-TISSUES, AML, EXPRESSION