Screening of IDH1 and IDH2 Gene Mutations in Adult Acute Myeloid Leukemia for Possible Targeted Therapy

Study Overview
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Brief Summary
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To assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and to explore their associations with the patients' clinical, cytogenetic, and molecular characteristics as well as with treatment response and outcome. To delineate the similarities and distinctions among mutations at IDH1-R132, IDH2-R140 and IDH2-R172 in AML, both clinically and molecularly (including cytogenetics, immunophenotyping, mutation co-occurrence patterns). The results can be references for future selection of targeted therapy (targeting IDH mutant proteins).

Detailed Description
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Isocitrate dehydrogenases (IDH) are enzymes that catalyze oxidative decarboxylation of isocitrate into alpha-ketoglutarate (α-KG). IDH1 and IDH2 mutations in AML give the enzymes neomorphic enzymatic activity to transform α-KG to D-2HG, an oncometabolite which acts as a competitive inhibitor of dioxygenases, and causes dysregulation of TET2 and histone demethylases, consequently leading to epigenetic reprogramming of a cell, blocking differentiation and contributing to a transformed phenotype, and leukemogenesis. Investigators plan to recruit 300 adult AML patients (newly diagnosed or relapsed). 10mL of peripheral blood or marrow blood will be obtained from routine practice blood/marrow sampling specimens (no extra venipuncture or bone marrow aspiration would be required) and sent for routine tests such as cytogenetics, immunophenotyping, and gene mutation analyses. IDH1 R132, IDH2 R140, and IDH2 R172 mutations will be screened by PCR followed by Sanger sequencing, as previously described. Investigators will first assess the incidence of IDH1 and IDH2 mutations in adult AML patients, and then explore their associations with the patients' clinical course, cytogenetic, and molecular characteristics as well as with treatment response and outcome. Investigators also seek to delineate the similarities and distinctions among IDH mutation variants at IDH1-R132, IDH2-R140 and IDH2-R172, both clinically and molecularly (including cytogenetics, immunophenotyping, mutation co-occurrence patterns).

Official Title
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Screening of IDH1 and IDH2 Gene Mutations in Adult Acute Myeloid Leukemia for Possible Targeted Therapy

Conditions
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Acute Myeloid Leukemia

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients ≥20 Years with Diagnosed Acute Myeloid Leukemia Willing to provide voluntary written informed consent before study related procedures Exclusion criteria: Not acute myeloid leukemia patients Patients <20 Years with Diagnosed Acute Myeloid Leukemia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of IDH1 and IDH2 mutation | Peripheral blood or marrow blood will be obtained from routine practice blood/marrow sampling specimens (no extra venipuncture or bone marrow aspiration would be required) and sent for routine tests such as cytogenetics, immunophenotyping, and gene mutation analyses. | 2017/03/07 - 2019/03/01 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukemia, IDH1, IDH2, Genetic mutations, Prognosis