FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.

Published

Journal Article

The clinical impact of FLT3-internal tandem duplications (ITDs), an adverse prognostic marker in adults aged < 60 years with primary cytogenetically normal acute myeloid leukemia (CN-AML), requires further investigation in older patients. In CN-AML patients aged ≥ 60 years treated on Cancer and Leukemia Group B frontline trials, we found that FLT3-ITD remained associated with shorter disease-free survival (P < .001; hazard ratio = 2.10) and overall survival (P < .001; hazard ratio = 1.97) in multivariable analyses. This impact on shorter disease-free survival and overall survival was in patients aged 60-69 (P < .001, each) rather than in those aged ≥ 70 years. An FLT3-ITD-associated gene-expression signature revealed overexpression of FLT3, homeobox genes (MEIS1, PBX3, HOXB3), and immunotherapeutic tar-gets (WT1, CD33) and underexpression of leukemia-associated (MLLT3, TAL1) and erythropoiesis-associated (GATA3, EPOR, ANK1, HEMGN) genes. An FLT3-ITD-associated microRNA-expression signature included overexpressed miR-155 and underexpressed miR-144 and miR-451. FLT3-ITD identifies older CN-AML patients with molecular high risk and is associated with gene- and microRNA-expression signatures that provide biologic insights for novel therapeutic approaches.

Full Text

Duke Authors

Cited Authors

  • Whitman, SP; Maharry, K; Radmacher, MD; Becker, H; Mrózek, K; Margeson, D; Holland, KB; Wu, Y-Z; Schwind, S; Metzeler, KH; Wen, J; Baer, MR; Powell, BL; Carter, TH; Kolitz, JE; Wetzler, M; Moore, JO; Stone, RM; Carroll, AJ; Larson, RA; Caligiuri, MA; Marcucci, G; Bloomfield, CD

Published Date

  • November 4, 2010

Published In

Volume / Issue

  • 116 / 18

Start / End Page

  • 3622 - 3626

PubMed ID

  • 20656931

Pubmed Central ID

  • 20656931

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2010-05-283648

Language

  • eng

Conference Location

  • United States