NDLI: Molecular alterations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes and additional genetic mutations in newly diagnosed acute myeloid leukemia patients

Content Provider	Springer Nature : BioMed Central
Author	Chotirat, Sadudee Thongnoppakhun, Wanna Promsuwicha, Orathai Boonthimat, Chetsada Auewarakul, Chirayu U
Abstract	Background Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes encode cytosolic and mitochondrial enzymes that catalyze the conversion of isocitrate to α-ketoglutarate. Acquired somatic mutations of IDH1 and IDH2 have recently been reported in some types of brain tumors and a small proportion of acute myeloid leukemia (AML) cases. Methods Two-hundred and thirty newly diagnosed AML patients were analyzed for the presence of IDH1 and IDH2 heterozygous mutations by polymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC) followed by direct sequencing. Clinical and biological characteristics were analyzed and correlated to the IDH mutational status. Coexisting mutations such as FLT3, PML- RARA, RAS, AML1, and NPM1 mutations were additionally explored. Results The prevalence of IDH1 and IDH2 mutations was 8.7% (20/230) and 10.4% (24/230), respectively. Six missense mutations were identified among IDH1-mutated cases; p.R132H (n = 8), p.R132C (n = 6), p.R132S (n = 2), p.R132G (n = 2), p.R132L (n = 1), and p.I99M (n = 1). Two missense mutations were found in IDH2-mutated cases; p.R140Q (n = 20) and p.R172K (n = 4). No patients had dual IDH1 and IDH2 mutations. About 18% of AML with normal cytogenetics and 31% of acute promyelocytic leukemia had IDH mutations. Half of the IDH-mutated cohort had normal karyotype and the major FAB subtype was AML-M2. Interestingly, IDH1- and IDH2-mutated cases predominantly had NPM1 mutations (60-74%) as compared to the wild type (P < 0.001). Very few IDH-mutated cases had FLT3 and/or RAS abnormalities and none of them had AML1 mutations. Older age and higher median platelet counts were significantly associated with IDH2 mutations although the clinical impact of either IDH1 or IDH2 mutations on patients' overall survival could not be observed. Conclusion Overall, 19% of newly diagnosed AML patients had alterations of IDH genes. No patients concurrently carried both IDH1 and IDH2 mutations suggesting that these mutations were mutually exclusive. NPM1 mutation appears as a major coexisting genetic mutation in IDH-mutated patients. Our present data failed to support the prognostic relevance of IDH mutations although alterations of these metabolic genes potentially have an important role in leukemia development.
Related Links	https://jhoonline.biomedcentral.com/counter/pdf/10.1186/1756-8722-5-5.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	17568722
DOI	10.1186/1756-8722-5-5
Journal	Journal of Hematology & Oncology
Issue Number	1
Volume Number	5
Language	English
Publisher	BioMed Central
Publisher Date	2012-03-07
Access Restriction	Open
Subject Keyword	Oncology Hematology Cancer Research IDH1 IDH2 Acute myeloid leukemia Isocitrate dehydrogenase Metabolic enzymes Cooperative mutations Normal karyotype
Content Type	Text
Resource Type	Article
Subject	Hematology Cancer Research Oncology Molecular Biology
Journal Impact Factor	29.9/2023
5-Year Journal Impact Factor	27.1/2023

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