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

Show simple item record 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 2020-03-05T11:17:01Z 2020-03-05T11:17:01Z 2020-02-11
dc.identifier.citation 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 .
dc.identifier.other PURE: 133169139
dc.identifier.other PURE UUID: 6c1f1864-673b-4171-99c4-1a3e85918401
dc.identifier.other WOS: 000513945400016
dc.identifier.other ORCID: /0000-0002-0816-8241/work/70951998
dc.identifier.other ORCID: /0000-0003-4112-5902/work/70953053
dc.identifier.other ORCID: /0000-0001-5056-4750/work/70953943
dc.description.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. en
dc.format.extent 14
dc.language.iso eng
dc.relation.ispartof Blood advances
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject STEM
dc.subject EXPRESSION
dc.subject CELLS
dc.subject SIGNATURES
dc.subject NEOPLASMS
dc.subject 3122 Cancers
dc.title Mutation accumulation in cancer genes relates to nonoptimal outcome in chronic myeloid leukemia en
dc.type Article
dc.contributor.organization Department of Clinical Chemistry and Hematology
dc.contributor.organization Hematologian yksikkö
dc.contributor.organization Department of Oncology
dc.contributor.organization HUS Comprehensive Cancer Center
dc.contributor.organization University of Helsinki
dc.contributor.organization TRIMM - Translational Immunology Research Program
dc.contributor.organization Research Programs Unit
dc.contributor.organization HUSLAB
dc.contributor.organization Department of Medical and Clinical Genetics
dc.contributor.organization Department of Pharmacology
dc.contributor.organization Faculty of Medicine
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Clinicum
dc.contributor.organization Medicum
dc.contributor.organization Digital Precision Cancer Medicine (iCAN)
dc.description.reviewstatus Peer reviewed
dc.relation.issn 2473-9529
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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