Evaluation of IDH1G105 polymorphism as prognostic marker in intermediate-risk AML.
Germline polymorphisms in genes mutated in acute myeloid leukemia (AML) may have prognostic impact. Therefore, the relevance of the polymorphism IDH1G105 (IDH1105(GGT) minor allele) was evaluated in the context of concomitant molecular mutations in a cohort of 507 AML cases with intermediate-risk cytogenetics. In addition, a cohort of 475 healthy controls was analyzed for this polymorphism. IDH1105(GGT) minor allele was found in 10 % of AML patients and 9 % of healthy controls. While no differences were seen with regard to cytomorphology or cytogenetics, immunophenotyping revealed significantly reduced expression of the progenitor marker CD34 in AML cases harboring IDH1105(GGT) minor allele. Cases with IDH1105(GGT) minor allele as compared to those with the IDH1105(GGC) major allele had significantly longer event-free survival (EFS) (median 16 vs 11 months, p = 0.013) which was most pronounced in the age group >60 years (median 14 vs 9 months, p = 0.007) and in the NPM1 mutated/FLT3-ITD/FLT3wt ratio <0.5 group (median 61 vs 13 months, p = 0.012). However, this association is not independent of other prognostic parameters, and we conclude that IDH1105(GGT) minor allele has to be considered in the context of the genetic background of the individual AML analyzed.
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany. annette.fasan@mll.com.
Annette
A
Fasan
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Claudia
C
Haferlach
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Christiane
C
Eder
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Tamara
T
Alpermann
Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universitat, Munich, Germany.|German Research Center for Environmental Health, Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Anne
A
Quante
German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.|German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
Annette
A
Peters
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Wolfgang
W
Kern
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Torsten
T
Haferlach
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377, Munich, Germany.
Susanne
S
Schnittger
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D018952:Antigens, CD34; D014408:Biomarkers, Tumor / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011110:Polymorphism, Genetic; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
AML; IDH1; IDH2; Polymorphism; Prognosis