Detection of Dual IDH1 and IDH2 Mutations by Targeted Next-Generation Sequencing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

The Journal of Molecular Diagnostics : JMD
Mia Y PlattValentina Nardi

Abstract

Studies in myeloid neoplasms have described recurrent IDH1 and IDH2 mutations as primarily mutually exclusive. Over a 6-month period of clinical testing with a targeted next-generation sequencing assay, we evaluated 92 patients with acute myeloid leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia and identified a subset of 21 patients (23%) who harbored mutations in either IDH1 or IDH2. Of the 21 patients with IDH mutations, 4 (19%) were found to have single nucleotide variants in both IDH1 and IDH2. An additional patient included in the study was found to have two different IDH2 mutations. The mutations were typically present at different variant allelic frequencies, with one predominating over the other, consistent with the presence of multiple subclones in a single patient. In one case, the variant allelic frequencies in both IDH1 and IDH2 were equally low in the setting of a high percentage of blasts, suggesting that the IDH mutations were unlikely to be present in the founding clone. Given these data, we conclude that dual IDH1/2 mutations likely were previously underestimated, a finding that may carry important treatment implications.

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Citations

Mar 5, 2016·Surgical Pathology Clinics·Valentina Nardi, Robert P Hasserjian
Oct 11, 2016·Leukemia·B C MedeirosR Swords
Mar 16, 2018·Future Oncology·Guillermo Montalban-Bravo, Courtney D DiNardo
Oct 25, 2017·Current Hematologic Malignancy Reports·Brittany Knick Ragon, Courtney D DiNardo
Apr 21, 2020·Expert Review of Hematology·Xavier ThomasMaël Heiblig
Sep 2, 2020·Expert Review of Hematology·Juan Eduardo Megías-VericatPau Montesinos
Aug 28, 2019·Expert Opinion on Pharmacotherapy·Maria Ilaria Del PrincipeAdriano Venditti
Jun 9, 2018·Cancers·Michael J BuegeCourtney D DiNardo
May 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maria L Amaya, Daniel A Pollyea
Nov 17, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Ana Bela Sarmento-RibeiroIoannis P Trougakos
Aug 19, 2021·European Journal of Haematology·Amy SongMohammad O Hussaini

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