Hierarchical distribution of somatic variants in newly diagnosed chronic myeloid leukaemia at diagnosis and early follow-up

Varování

Publikace nespadá pod Filozofickou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	ROMŽOVÁ Marianna SMITALOVÁ Dagmar HYNŠT Jakub TOM Nikola LOJA Tomáš HERUDKOVÁ Zdeňka JURČEK Tomáš STEJSKAL Lukas ŽÁČKOVÁ Daniela MAYER Jiří RÁČIL Zdeněk ČULEN Martin
Rok publikování	2021
Druh	Článek v odborném periodiku
Časopis / Zdroj	British journal of haematology
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	https://onlinelibrary.wiley.com/doi/10.1111/bjh.17659
Doi	http://dx.doi.org/10.1111/bjh.17659
Klíčová slova	CML; NGS; progenitors; leukaemic stem cells; somatic mutations; ASXL1
Popis	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.
Související projekty:	Mutační analýza primitivních buněčných populací u chronické myeloidní leukémie: za hranicí BCR-ABL1 Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VIII