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
Source: PubMed

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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    Bioinformatics 05/2014; 30(17). DOI:10.1093/bioinformatics/btu339 · 4.62 Impact Factor
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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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    ABSTRACT: Background Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique. Aim of the work The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML. Methods Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations screening. Results The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p = 0.03). Patients with IDH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p = 0.08). Conclusion IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDH1 mutations in AML.
    Journal of the Egyptian National Cancer Institute 01/2013; 26(1). DOI:10.1016/j.jnci.2013.11.001
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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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    ABSTRACT: Mutations of isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (R132H), have been described in World Health Organization grade II and III diffuse gliomas and secondary glioblastoma. Immunohistochemistry using a mouse monoclonal antibody has a high specificity and sensitivity for detecting IDH1 R132H mutant protein in sections from formalin-fixed, paraffin-embedded tissue. Angiocentric glioma (AG), a unique neoplasm with mixed phenotypic features of diffuse glioma and ependymoma, has recently been codified as a grade I neoplasm in the 2007 World Health Organization classification of central nervous system tumors. The present study was designed to evaluate IDH1 R132H protein in AG. Three cases of AG were collected, and the diagnoses were confirmed. Expression of mutant IDH1 R132H protein was determined by immu-nohistochemistry on representative formalin-fixed, paraffin-embedded sections using the antihuman mouse monoclonal antibody IDH1 R132H (Dianova, Hamburg, Germany). Known IDH1 mutation– positive and IDH1 wild-type cases of grade II to IV glioma served as positive and negative controls. All 3 patients were male, aged 3, 5, and 15 years, with intra-axial tumors in the right posterior parietal-occipital lobe, right frontal lobe, and left frontal lobe, respectively. All 3 cases showed characteristic morphologic features of AG, including a monomorphous population of slender bipolar cells that diffusely infiltrated cortical parenchyma and ensheathed cortical blood vessels radially and longitudinally. All 3 cases were negative for the presence of IDH1 R132H mutant protein (0/3). All control cases showed appropriate reactivity. IDH1 R132H mutation has been described as a common molecular signature of grade II and III diffuse gliomas and secondary glioblastoma; however, AG, which exhibits some features of diffuse glioma, has not been evaluated. The absence of mutant IDH1 R132H protein expression in AG may help further distinguish this unique neoplasm from diffuse glioma.
    Annals of Diagnostic Pathology 08/2012; 16:255-259. · 1.11 Impact Factor
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