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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.

Publication ,  Journal Article
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 ...
Published in: Blood
November 4, 2010

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.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

November 4, 2010

Volume

116

Issue

18

Start / End Page

3622 / 3626

Location

United States

Related Subject Headings

  • fms-Like Tyrosine Kinase 3
  • Survival Analysis
  • Prognosis
  • Middle Aged
  • MicroRNAs
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Gene Expression Regulation, Leukemic
 

Citation

APA
Chicago
ICMJE
MLA
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Whitman, S. P., Maharry, K., Radmacher, M. D., Becker, H., Mrózek, K., Margeson, D., … Bloomfield, C. D. (2010). 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. Blood, 116(18), 3622–3626. https://doi.org/10.1182/blood-2010-05-283648
Whitman, Susan P., Kati Maharry, Michael D. Radmacher, Heiko Becker, Krzysztof Mrózek, Dean Margeson, Kelsi B. Holland, et al. “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.Blood 116, no. 18 (November 4, 2010): 3622–26. https://doi.org/10.1182/blood-2010-05-283648.
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. 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. Blood. 2010 Nov 4;116(18):3622–3626.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

November 4, 2010

Volume

116

Issue

18

Start / End Page

3622 / 3626

Location

United States

Related Subject Headings

  • fms-Like Tyrosine Kinase 3
  • Survival Analysis
  • Prognosis
  • Middle Aged
  • MicroRNAs
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Gene Expression Regulation, Leukemic