American Association for Cancer Research
Browse
00085472can093783-sup-can_1-15-10_abdel-wahab.pdf (22.53 kB)

Supplementary Tables 1-3 from Genetic Analysis of Transforming Events That Convert Chronic Myeloproliferative Neoplasms to Leukemias

Download (22.53 kB)
journal contribution
posted on 2023-03-30, 19:42 authored by Omar Abdel-Wahab, Taghi Manshouri, Jay Patel, Kelly Harris, JinJuan Yao, Cyrus Hedvat, Adriana Heguy, Carlos Bueso-Ramos, Hagop Kantarjian, Ross L. Levine, Srdan Verstovsek
Supplementary Tables 1-3 from Genetic Analysis of Transforming Events That Convert Chronic Myeloproliferative Neoplasms to Leukemias

History

ARTICLE ABSTRACT

The oncogenetic events that transform chronic myeloproliferative neoplasms (MPN) to acute myeloid leukemias (AML) are not well characterized. We investigated the role of several genes implicated in leukemic transformation by mutational analysis of 63 patients with AML secondary to a preexisting MPN (sAML). Frequent mutations were identified in TET2 (26.3%), ASXL1 (19.3%), IDH1 (9.5%), and JAK2 (36.8%) mutations in sAML, and all possible mutational combinations of these genes were also observed. Analysis of 14 patients for which paired samples from MPN and sAML were available showed that TET2 mutations were frequently acquired at leukemic transformation [6 of 14 (43%)]. In contrast, ASXL1 mutations were almost always detected in both the MPN and AML clones from individual patients. One case was also observed where TET2 and ASXL1 mutations were found before the patient acquired a JAK2 mutation or developed clinical evidence of MPN. We conclude that mutations in TET2, ASXL1, and IDH1 are common in sAML derived from a preexisting MPN. Although TET2/ASXL1 mutations may precede acquisition of JAK2 mutations by the MPN clone, mutations in TET2, but not ASXL1, are commonly acquired at the time of leukemic transformation. Our findings argue that the mutational order of events in MPN and sAML varies in different patients, and that TET2 and ASXL1 mutations have distinct roles in MPN pathogenesis and leukemic transformation. Given the presence of sAML that have no preexisting JAK2/TET2/ASXL1/IDH1 mutations, our work indicates the existence of other mutations yet to be identified that are necessary for leukemic transformation. Cancer Res; 70(2); 447–52

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC