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: 2.51). 01/2011; 135(1):35-45. DOI: 10.1309/AJCPD7NR2RMNQDVF
Source: PubMed


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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    • "This study sparked research into the field of IDH1 mutations within various AML populations, particularly the frequency of mutations and their clinical significance. To date there the approximate rate of IDH1 mutations in Western countries including the United States[3], [4], [5], Canada[6], France[7], Germany[8], [9], [10], [11], Netherlands[12] and England[13], [14] is 10–14%. However, there are limited reports regarding the rate of IDH1 mutations in Chinese AML patients suggest a mutation rate of 2–6.3%. "
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    • "For IDH1R132 mutations in AML, as in other tumors, five major different amino acid substitutions for arginine (R) have been detected: cysteine (R132C), leucine (R132L), glycine (R132G), histidine (R132H), and serine (R132S) (Mardis et al., 2009; Abbas et al., 2010; Chou et al., 2010; Ho et al., 2010; Marcucci et al., 2010; Schnittger et al., 2010; Wagner et al., 2010; Patel et al., 2011a). R132C (∼30%) and R132H (∼50%) are the most common mutations in AML. "
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