Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia

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Awad , S A , Kankainen , M , Ojala , T , Koskenvesa , P , Eldfors , S , Ghimire , B , Kumar , A , Kytölä , S , Kamel , M M , Heckman , C A , Porkka , K & Mustjoki , S 2020 , ' Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia ' , Blood advances , vol. 4 , no. 3 , pp. 546-559 .

Title: Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia
Author: Awad, Shady Adnan; Kankainen, Matti; Ojala, Teija; Koskenvesa, Perttu; Eldfors, Samuli; Ghimire, Bishwa; Kumar, Ashwini; Kytölä, Soili; Kamel, Mahmoud M.; Heckman, Caroline A.; Porkka, Kimmo; Mustjoki, Satu
Contributor organization: Department of Clinical Chemistry and Hematology
Hematologian yksikkö
Department of Oncology
HUS Comprehensive Cancer Center
University of Helsinki
TRIMM - Translational Immunology Research Program
Research Programs Unit
Department of Medical and Clinical Genetics
Department of Pharmacology
Faculty of Medicine
Institute for Molecular Medicine Finland
Digital Precision Cancer Medicine (iCAN)
Date: 2020-02-11
Language: eng
Number of pages: 14
Belongs to series: Blood advances
ISSN: 2473-9529
Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm accounting for similar to 15% of all leukemia. Progress of the disease from an indolent chronic phase to the more aggressive accelerated phase or blast phase (BP) occurs in a minority of cases and is associated with an accumulation of somatic mutations. We performed genetic profiling of 85 samples and transcriptome profiling of 12 samples from 59 CML patients. We identified recurrent somatic mutations in ABL1 (37%), ASXL1 (26%), RUNX1 (16%), and BCOR (16%) in the BP and observed that mutation signatures in the BP resembled those of acute myeloid leukemia (AML). We found that mutation load differed between the indolent and aggressive phases and that nonoptimal responders had more nonsilent mutations than did optimal responders at the time of diagnosis, as well as in follow-up. Using RNA sequencing, we identified other than BCR-ABL1 cancer-associated hybrid genes in 6 of the 7 BP samples. Uncovered expression alterations were in turn associated with mechanisms and pathways that could be targeted in CML management and by which somatic alterations may emerge in CML. Last, we showed the value of genetic data in CML management in a personalized medicine setting.
3122 Cancers
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion

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