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@article{1786441,
author = {Romžová, Marianna and Smitalová, Dagmar and Hynšt, Jakub and Tom, Nikola and Loja, Tomáš and Herudková, Zdeňka and Jurček, Tomáš and Stejskal, Lukas and Žáčková, Daniela and Mayer, Jiří and Ráčil, Zdeněk and Čulen, Martin},
article_location = {Hoboken},
article_number = {3},
doi = {http://dx.doi.org/10.1111/bjh.17659},
keywords = {CML; NGS; progenitors; leukaemic stem cells; somatic mutations; ASXL1},
language = {eng},
issn = {0007-1048},
journal = {British journal of haematology},
title = {Hierarchical distribution of somatic variants in newly diagnosed chronic myeloid leukaemia at diagnosis and early follow-up},
url = {https://onlinelibrary.wiley.com/doi/10.1111/bjh.17659},
volume = {194},
year = {2021}
}
TY - JOUR
ID - 1786441
AU - Romžová, Marianna - Smitalová, Dagmar - Hynšt, Jakub - Tom, Nikola - Loja, Tomáš - Herudková, Zdeňka - Jurček, Tomáš - Stejskal, Lukas - Žáčková, Daniela - Mayer, Jiří - Ráčil, Zdeněk - Čulen, Martin
PY - 2021
TI - Hierarchical distribution of somatic variants in newly diagnosed chronic myeloid leukaemia at diagnosis and early follow-up
JF - British journal of haematology
VL - 194
IS - 3
SP - 604-612
EP - 604-612
PB - Wiley-Blackwell
SN - 00071048
KW - CML
KW - NGS
KW - progenitors
KW - leukaemic stem cells
KW - somatic mutations
KW - ASXL1
UR - https://onlinelibrary.wiley.com/doi/10.1111/bjh.17659
N2 - 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.
ER -
ROMŽOVÁ, Marianna, Dagmar SMITALOVÁ, Jakub HYNŠT, Nikola TOM, Tomáš LOJA, Zdeňka HERUDKOVÁ, Tomáš JURČEK, Lukas STEJSKAL, Daniela ŽÁČKOVÁ, Jiří MAYER, Zdeněk RÁČIL and Martin ČULEN. Hierarchical distribution of somatic variants in newly diagnosed chronic myeloid leukaemia at diagnosis and early follow-up. \textit{British journal of haematology}. Hoboken: Wiley-Blackwell, 2021, vol.~194, No~3, p.~604-612. ISSN~0007-1048. Available from: https://dx.doi.org/10.1111/bjh.17659.
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