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Acute Myeloid Leukemia With IDH1 or IDH2 Mutation Frequency and Clinicopathologic Features

Dept of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
American Journal of Clinical Pathology (Impact Factor: 3.01). 01/2011; 135(1):35-45. DOI: 10.1309/AJCPD7NR2RMNQDVF
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ABSTRACT Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are reported in acute myeloid leukemia (AML). We studied the frequency and the clinicopathologic features of IDH1 and IDH2 mutations in AML. Mutations in IDH1 (IDH1(R)¹³²) and IDH2 (IDH2(R)¹⁷²) were assessed by Sanger sequencing in 199 AML cases. Point mutations in IDH1(R)¹³² were detected in 12 (6.0%) of 199 cases and in IDH2(R)¹⁷² in 4 (2.0%) of 196 cases. Of the 16 mutated cases, 15 (94%) were cytogenetically normal, for an overall frequency in this group of 11.8%. IDH1(R)¹³² and IDH2(R)¹⁷² mutations were mutually exclusive. Concurrent mutations in NPM1, FLT3, CEBPA, and NRAS were detected only in AML with the IDH1(R)¹³² mutation. The clinical and laboratory variables of patients with AML with IDH mutations showed no significant differences compared with patients with wild-type IDH. We conclude that IDH1(R)¹³² and IDH2(R)¹⁷² mutations occur most often in cytogenetically normal AML cases with an overall frequency of approximately 11.8%.

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Available from: Farhad Ravandi, Mar 17, 2014
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    • " the clinical and molecular stand - points , with many distinct molecular subtypes defined by genetic abnormalities ; several of these target key epigenetic regulators . An estimated 20% - 25% of all AMLs are associated with heterozygous somatic mutations of isocitrate dehydrogenase 1 or 2 ( IDH1 or 2 ) , or ten - eleven translocation 2 ( TET2 ) ( Patel et al . , 2011 ) . Any one of these mutations results in an impairment of DNA demethylation pathways and leads to the establishment of a DNA hypermethylation phenotype ( Figueroa et al . , 2010a ) . A separate class of AMLs , con - stituting approximately 15% of all AML cases , are identified by the presence of the t ( 8 ; 21 ) translocation giving ri"
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    • "In fact, IDH1 was significantly less frequent in patients with activating FLT3-ITD mutation. Our findings were however similar to other studies [6] [25] [28]. "
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    • "This mutation is rare in primary glioblastoma and other primary central nervous system tumors and is absent in classical gliomatosis cerebri and ependymoma [3] [4] [17] [19] [21] [22]. IDH1 R132H mutation is also very rare in systemic malignancies in general, with the notable exception of acute myeloid leukemia, in which R132H is present in 6% to 7% of cases [34] [35] [36] [37]. Most IDH1 mutations are single-base substitutions, with G395A present in about 90% of cases, resulting in substitution of histidine for arginine at position 132 (R132H) [2] [17] [19] [20]. "
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