Molecular Evaluation of DNMT3A and IDH1/2 Gene Mutation: Frequency, Distribution Pattern and Associations with Additional Molecular Markers in Normal Karyotype Indian Acute Myeloid Leukemia Patients

Ahmad, Firoz; Mohota, Rupali; Sanap, Savita; Mandava, Swarna; Das, Bibhu Ranjan

doi:10.7314/apjcp.2014.15.3.1247

Cited by 25 publications

(13 citation statements)

References 46 publications

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“…However, in another study, IDH1 and 2 mutations were detected in 5.5% and 4%, respectively (Raveendran et al, 2015). Some reports found the frequency of IDH1 mutations in AML patients from various countries 2-14% (Chotirat et al, 2012;Ahmad et al, 2014). In the present study, we have found that IDH1 and IDH2 mutations were mutually exclusive as previously reported (Papaemmanuil et al, 2016).…”

Section: Molecular Mutationssupporting

confidence: 83%

IDH Mutations in AML Patients; A higher Association with Intermediate Risk Cytogenetics

Elnahass

Badawy

Elrefaey

et al. 2020

Asian Pac J Cancer Prev

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Objective: IDH mutations diversely affect the prognosis of cyogenetically normal acute myeloid leukemia (CN-AML) adult patients. The aim of this study is to assess the frequency of IDH mutations and to evaluate its role in AML prognosis. Methods: We have analyzed IDH1 and 2 mutations using High Resolution Melting curve analysis (HRM) in 70 denovo AML patients. Results: The median age of AML patients is 40 years (16-75). Incidence of IDH mutations is 10/70 (14.3%); 2 (2.9%) IDH1 mutant and 8 (11.4%) IDH2 mutant. Median PB blasts of mutant IDH patients was 67.5% (25-96) vs. 44% (0-98) for wild type (p=0.065). Eight/10 (80%) mutant IDH patients had B.M blasts ≥50% vs. 2/10 (20%) <50% (p<0.001) and were classified as intermediate risk cytogenetics (p=0.020) with wild FLT3-ITD (p=0.001). Ten/10 (100%) mutant IDH patients showed wild NPM1 (p=0.049). Median OS of mutant IDH in the intermediate risk cytogenetics was 1.8 years (0.7-3.1) vs. 3.1 years (1.1-5.5) for wild IDH (p=0.05). Conclusion: IDH mutation is mainly associated with intermediate risk AML and when integrated in this specific subgroup displays a lower survival and can be considered an additional integrated molecular risk marker for AML prognosis.

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Section: Molecular Mutationssupporting

confidence: 83%

IDH Mutations in AML Patients; A higher Association with Intermediate Risk Cytogenetics

Elnahass

Badawy

Elrefaey

et al. 2020

Asian Pac J Cancer Prev

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“…The frequency of DNMT3A mutations varies from 15% to 40% in AML de novo. Several recent studies have reported an association between DNMT3A mutation and Flt3mut and have a poor clinical outcome in AML patients [2]. In this case we report one single-nucleotide polymorphism L901L, c.2703C>T, and no mutation in Flt3.…”

Section: Case Reportmentioning

confidence: 45%

Acute Leukemia Trilineage Blasts Assignment and Epigenetic Mutations

Amal¹,

Subota²,

Mbarka³

et al. 2017

J Bone Res

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Mixed Phenotype Acute Leukaemia (MPAL) is a heterogeneous group of rare leukemias in which assigning a single lineage of origin is not possible. We report a rare case of a MPAL without any clear cytological characterisation. Immuno-phenotyping identifies a blastic population co-expressing myeloid, B-lymphoid and T-lymphoid markers. The diagnosis of MPAL is considered and the patient receives chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation. DNA-based techniques analyzing B and T-cell clonality identified the presence of partial rearrangements in immunoglobulin and TCR genes. Mutations in DNMT3A, IDH1/2, Flt3, NPM1 and ASXL1 genes were analysed.We did not observe any mutations in IDH2, Flt3 and ASXL1 genes. A several mutations were in DNMT3A, IDH1 and NPM1 genes, allowing the monitoring of minimal residual disease.

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“…DNA segments that were sequenced were: exon 17/18 of DNMT3A (NM_175629.2) (Ahmad et al 2014), exon 4 of IDH1 (NM_001282387.1) (Yan et al 2009), exon 11 of IDH2 (NM_002168.3) (Ahmad et al 2014), exon 13–16 of SF3B1 (NG_032903.2) (Brecqueville et al 2012; Rossi et al 2011), exon 1 of SRSF2 (NM_003016.4) (Patnaik et al 2013), and exon 2/6 of U2AF1 (NM_001025203.1) (Patnaik et al 2013). …”

Section: Methodsmentioning

confidence: 99%

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

Ren

Zhou

et al. 2017

J Cancer Res Clin Oncol

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PurposeThe aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes—refractory anemia with excess of blasts (MDS-RAEB).MethodsThe current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens.ResultsA total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2–21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at < 60 years of age, the CR rate in the decitabine priming group was significantly higher than in the chemotherapy group (65.5 vs. 31.0%, p = 0.009). Survival benefit of decitabine priming was apparent in patients at < 60 years of age (22.4 months with 95% CI of 6.7–38.1 vs. 14.7 months with 95% CI of 11.4–18.0 months in the chemotherapy group, p = 0.028), patients with intermediate and unfavorable karyotypes (22.4 months with 95% CI of 15.1–29.7 vs. 11.9 months with 95% CI of 4.0–19.8 months in the chemotherapy group, p = 0.042), and patients with mutated splicing factor genes (35.3 months with 95% CI of 21.4–49.2 vs. 17.8 months with 95% CI of 13.8–21.8 months in the chemotherapy group, p = 0.039). Grade 3–4 hematological and non-hematological toxicities were not significantly different between the two groups.ConclusionsDecitabine priming prior to low-dose chemotherapy could improve treatment responses in patients with MDS-RAEB.

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Molecular Evaluation of DNMT3A and IDH1/2 Gene Mutation: Frequency, Distribution Pattern and Associations with Additional Molecular Markers in Normal Karyotype Indian Acute Myeloid Leukemia Patients

Cited by 25 publications

References 46 publications

IDH Mutations in AML Patients; A higher Association with Intermediate Risk Cytogenetics

IDH Mutations in AML Patients; A higher Association with Intermediate Risk Cytogenetics

Acute Leukemia Trilineage Blasts Assignment and Epigenetic Mutations

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

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