Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study

被引：80

作者：

Ho, P. A. ^{[1
,2
]}

Alonzo, T. A. ^{[3
]}

Kopecky, K. J. ^{[4
]}

Miller, K. L. ^{[1
]}

Kuhn, J. ^{[1
]}

Zeng, R. ^{[1
]}

Gerbing, R. B. ^{[5
]}

Raimondi, S. C. ^{[6
]}

Hirsch, B. A. ^{[7
]}

Oehler, V. ^{[1
,8
]}

Hurwitz, C. A. ^{[9
]}

Franklin, J. L. ^{[10
,11
]}

Gamis, A. S. ^{[12
]}

Petersdorf, S. H. ^{[8
]}

Anderson, J. E. ^{[13
]}

Reaman, G. H. ^{[14
]}

Baker, L. H. ^{[15
]}

Willman, C. L. ^{[16
]}

Bernstein, I. D. ^{[1
,2
]}

Radich, J. P. ^{[1
,8
]}

Appelbaum, F. R. ^{[1
,8
]}

Stirewalt, D. L. ^{[1
,8
]}

Meshinchi, S. ^{[1
,2
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA

[2] Univ Washington, Sch Med, Div Pediat Hematol Oncol, Seattle, WA USA

[3] Univ So Calif, Keck Sch Med, Dept Biostat, Los Angeles, CA 90033 USA

[4] Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA

[5] Childrens Oncol Grp, Arcadia, CA USA

[6] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA

[7] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[8] Univ Washington, Sch Med, Div Med Oncol, Seattle, WA USA

[9] Reata Pharma, Clin Dev, Dallas, TX USA

[10] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA

[11] Amgen Inc, Thousand Oaks, CA 91320 USA

[12] Childrens Mercy Hosp & Clin, Div Hematol Oncol, Kansas City, MO USA

[13] Katmai Oncol Grp, Anchorage, AK USA

[14] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA

[15] Univ Michigan, Sch Med, Ann Arbor, MI USA

[16] Univ New Mexico, Canc Res & Treatment Ctr, UNM Canc Res Facil, Albuquerque, NM 87131 USA

来源：

LEUKEMIA | 2010年 / 24卷 / 05期

基金：

美国国家卫生研究院;

关键词：

acute myeloid leukemia; IDH1; isocitrate dehydrogenase; pediatric AML; NPM; FLT3; ACUTE MYELOID-LEUKEMIA; CODON; 132; MUTATIONS; GLIOMAS; TUMORS; CYTARABINE; THERAPY; ADULTS; FLT3;

D O I：

10.1038/leu.2010.56

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent whole-genome sequencing efforts led to the identification of IDH1(R132) mutations in acute myeloid leukemia (AML) patients. We studied the prevalence and clinical implications of IDH1 genomic alterations in pediatric and adult AML. Diagnostic DNA from 531 AML patients treated on Children's Oncology Group trial COG-AAML03P1 (N=257), and Southwest Oncology Group trials SWOG-9031, SWOG-9333 and SWOG-9500 (N=274), were tested for IDH1 mutations. Codon R132 mutations were absent in the pediatric cohort, but were found in 12 of 274 adult patients (4.4%, 95% CI 2.3-7.5). IDH1(R132) mutations occurred most commonly in patients with normal karyotype, and those with FLT3/ITD and NPMc mutations. Patients with IDH1(R132) mutations trended toward higher median diagnostic white blood cell counts (59.2 x 10(9) vs 29.1 x 10(9) per liter, P=0.19) than those without mutations, but the two groups did not differ significantly in age, bone marrow blast percentage, overall survival or relapse-free survival. Eleven patients (2.1%) harbored a novel V71I sequence alteration, which was found to be a germ-line polymorphism. IDH1 mutations were not detected in pediatric AML, and are uncommon in adult AML. Leukemia (2010) 24, 909-913; doi:10.1038/leu.2010.56; published online 8 April 2010

引用

页码：909 / 913

页数：5

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