Hierarchical distribution of somatic variants in newly diagnosed chronic myeloid leukaemia at diagnosis and early follow-up
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
34212373
DOI
10.1111/bjh.17659
Knihovny.cz E-resources
- Keywords
- ASXL1, CML, NGS, leukaemic stem cells, progenitors, somatic mutations,
- MeSH
- Fusion Proteins, bcr-abl genetics MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis genetics therapy MeSH
- Humans MeSH
- Mutation MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Prospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fusion Proteins, bcr-abl MeSH
- BCR-ABL1 fusion protein, human MeSH Browser
There is an emerging body of evidence that patients with chronic myeloid leukaemia (CML) may carry not only breakpoint cluster region-Abelson murine leukaemia viral oncogene homologue 1 (BCR-ABL1) kinase domain mutations (BCR-ABL1 KD mutations), but also mutations in other genes. Their occurrence is highest during progression or at failure, but their impact at diagnosis is unclear. In the present study, we prospectively screened for mutations in 18 myeloid neoplasm-associated genes and BCR-ABL1 KD in the following populations: bulk leucocytes, CD34+ CD38+ progenitors and CD34+ CD38- stem cells, at diagnosis and early follow-up. In our cohort of chronic phase CML patients, nine of 49 patients harboured somatic mutations in the following genes: six ASXL1 mutations, one SETBP1, one TP53, one JAK2, but no BCR-ABL1 KD mutations. In seven of the nine patients, mutations were detected in multiple hierarchical populations including bulk leucocytes at diagnosis. The mutation dynamics reflected the BCR-ABL1 transcript decline induced by treatment in eight of the nine cases, suggesting that mutations were acquired in the Philadelphia chromosome (Ph)-positive clone. In one patient, the JAK2 V617F mutation correlated with a concomitant Ph-negative myeloproliferative neoplasm and persisted despite a 5-log reduction of the BCR-ABL1 transcript. Only two of the nine patients with mutations failed first-line therapy. No correlation was found between the mutation status and survival or response outcomes.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Hemato Oncology University Hospital Ostrava Czech Republic
Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
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