Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

被引:44
|
作者
Schwind, Sebastian [1 ]
Marcucci, Guido [1 ,2 ]
Kohlschmidt, Jessica [1 ,3 ]
Radmacher, Michael D. [1 ,3 ]
Mrozek, Krzysztof [1 ]
Maharry, Kati [1 ,3 ]
Becker, Heiko [1 ]
Metzeler, Klaus H. [1 ]
Whitman, Susan P. [1 ]
Wu, Yue-Zhong [1 ]
Powell, Bayard L. [4 ]
Baer, Maria R. [5 ,6 ]
Kolitz, Jonathan E. [7 ]
Carroll, Andrew J. [8 ]
Larson, Richard A. [9 ]
Caligiuri, Michael A. [1 ,2 ]
Bloomfield, Clara D. [1 ]
机构
[1] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Microbiol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA
[3] Duke Univ, Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA
[4] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA
[5] Univ Maryland, Dept Med, Baltimore, MD 21201 USA
[6] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[7] N Shore Univ Hosp, Manhasset, NY USA
[8] Univ Alabama Birmingham, Birmingham, AL USA
[9] Univ Chicago, Chicago, IL 60637 USA
关键词
INTERNAL TANDEM DUPLICATION; ETS-RELATED GENE; DISTINCT GENE; PROGNOSTIC IMPACT; YOUNGER ADULTS; CANCER; MICRORNA; MUTATIONS; PREDICTS; FLT3;
D O I
10.1182/blood-2011-06-357764
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Low MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (>= 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene-embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets. (Blood. 2011;118(15):4188-4198)
引用
收藏
页码:4188 / 4198
页数:11
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