Impact of IDH1 R132 Mutations and an IDH1 Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor

Abstract

IDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in CN-AML.

Prognostic implications and molecular associations of NADH dehydrogenase subunit 4 (ND4) mutations in acute myeloid leukemia

“…20,24 Genomic and mitochondrial DNA were extracted from samples using the All Prep DNA/RNA Kit (Qiagen, Hilden, Germany) according to the manufacturer's recommendations. Complete coverage of the mitochondrial ND4 gene sequence was accomplished using three overlapping PCR.…”

A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

“…1 We recently investigated hematopoiesis in Wnt3a-deficient mice. 2 Due to early embryonic lethality, 3 this analysis was performed in fetal liver (FL) at embryonic day 12.5. Remarkably, Wnt3a deficiency leads to reduced numbers of long-term HSC and multipotent progenitors, which are severely and irreversibly impaired in long-term reconstitution capacity as observed in serial transplantation assays.…”

“…1 Very recently, a series of reports about this mutation in AML have been published in a cluster of manuscripts. [1][2][3][4][5][6][7] As IDH1 mutation brings prognostic information in glioma and possibly AML, 4,[8][9] identification of IDH1 R132 mutations will bring increasing clinical relevance. Moreover, the mutation seems quite stable and may serve as a marker for monitoring minimal residual disease.…”

“…[1][2][3][4][5][6][7] Another upstream forward primer was used to generate a product as an internal control. Combination of these 7 forward primers and a common reverse primer ( Figure 1A) would generate a shorter mutant and a longer control product in any genomic DNA containing any type of R132 mutation, whereas only the longer product would be seen in samples without this mutation ( Figure 1B).…”

IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis

“…The first reports came from studies in AML. Initially uncovered by a whole-genome sequencing survey, 21 the IDH1 R132C mutation was subsequently searched in large cohorts of primary AML cases 1,[21][22][23][24][25][26][27] and was found to be detectable in a proportion of patients varying from 4.4 to 14%. Some of these studies also identified mutations affecting IDH2 R172 in 1.1-3.6% of cases, and a novel R140Q mutation in 6-15.6% of cases.…”