Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00079610" target="_blank" >RIV/65269705:_____/24:00079610 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/24:00135726
Result on the web
<a href="https://ashpublications.org/bloodadvances/article/8/10/2361/515202/Mutations-in-myeloid-transcription-factors-and" target="_blank" >https://ashpublications.org/bloodadvances/article/8/10/2361/515202/Mutations-in-myeloid-transcription-factors-and</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/bloodadvances.2023012127" target="_blank" >10.1182/bloodadvances.2023012127</a>
Alternative languages
Result language
angličtina
Original language name
Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes
Original language description
Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes, with a limit of detection of 0.2%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In conclusion, mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression and may help upfront TKI selection. (C) 2024 by The American Society of Hematology.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30205 - Hematology
Result continuities
Project
—
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood Advances
ISSN
2473-9529
e-ISSN
2473-9537
Volume of the periodical
8
Issue of the periodical within the volume
10
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
12
Pages from-to
2361-2372
UT code for WoS article
001293872300001
EID of the result in the Scopus database
2-s2.0-85195077302