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ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category.

Publication ,  Journal Article
Metzeler, KH; Becker, H; Maharry, K; Radmacher, MD; Kohlschmidt, J; Mrózek, K; Nicolet, D; Whitman, SP; Wu, Y-Z; Schwind, S; Powell, BL ...
Published in: Blood
December 22, 2011

The associations of mutations in the enhancer of trithorax and polycomb family gene ASXL1 with pretreatment patient characteristics, outcomes, and gene-/microRNA-expression profiles in primary cytogenetically normal acute myeloid leukemia (CN-AML) are unknown. We analyzed 423 adult patients for ASXL1 mutations, other prognostic gene mutations, and gene-/microRNA-expression profiles. ASXL1 mutations were 5 times more common in older (≥ 60 years) patients (16.2%) than those younger than 60 years (3.2%; P < .001). Among older patients, ASXL1 mutations associated with wild-type NPM1 (P < .001), absence of FLT3-internal tandem duplications (P = .002), mutated CEBPA (P = .01), and with inferior complete remission (CR) rate (P = .04), disease-free survival (DFS; P = .03), overall survival (OS; P = .006), and event-free survival (EFS; P = .002). Within the European LeukemiaNet (ELN) genetic categories of older CN-AML, ASXL1 mutations associated with inferior CR rate (P = .02), OS (P < .001), and EFS (P < .001) among ELN Favorable, but not among ELN Intermediate-I patients. Multivariable analyses confirmed associations of ASXL1 mutations with unfavorable CR rate (P = .03), DFS (P < .001), OS (P < .001), and EFS (P < .001) among ELN Favorable patients. We identified an ASXL1 mutation-associated gene-expression signature, but no microRNA-expression signature. This first study of ASXL1 mutations in primary CN-AML demonstrates that ASXL1-mutated older patients, particularly within the ELN Favorable group, have unfavorable outcomes and may be candidates for experimental treatment approaches.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 22, 2011

Volume

118

Issue

26

Start / End Page

6920 / 6929

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Risk Factors
  • Repressor Proteins
  • Prognosis
  • Oligonucleotide Array Sequence Analysis
  • Nucleophosmin
  • Mutation
  • Multivariate Analysis
  • Middle Aged
  • MicroRNAs
 

Citation

APA
Chicago
ICMJE
MLA
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Metzeler, K. H., Becker, H., Maharry, K., Radmacher, M. D., Kohlschmidt, J., Mrózek, K., … Bloomfield, C. D. (2011). ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood, 118(26), 6920–6929. https://doi.org/10.1182/blood-2011-08-368225
Metzeler, Klaus H., Heiko Becker, Kati Maharry, Michael D. Radmacher, Jessica Kohlschmidt, Krzysztof Mrózek, Deedra Nicolet, et al. “ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category.Blood 118, no. 26 (December 22, 2011): 6920–29. https://doi.org/10.1182/blood-2011-08-368225.
Metzeler KH, Becker H, Maharry K, Radmacher MD, Kohlschmidt J, Mrózek K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood. 2011 Dec 22;118(26):6920–9.
Metzeler, Klaus H., et al. “ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category.Blood, vol. 118, no. 26, Dec. 2011, pp. 6920–29. Pubmed, doi:10.1182/blood-2011-08-368225.
Metzeler KH, Becker H, Maharry K, Radmacher MD, Kohlschmidt J, Mrózek K, Nicolet D, Whitman SP, Wu Y-Z, Schwind S, Powell BL, Carter TH, Wetzler M, Moore JO, Kolitz JE, Baer MR, Carroll AJ, Larson RA, Caligiuri MA, Marcucci G, Bloomfield CD. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood. 2011 Dec 22;118(26):6920–6929.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 22, 2011

Volume

118

Issue

26

Start / End Page

6920 / 6929

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Risk Factors
  • Repressor Proteins
  • Prognosis
  • Oligonucleotide Array Sequence Analysis
  • Nucleophosmin
  • Mutation
  • Multivariate Analysis
  • Middle Aged
  • MicroRNAs