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

J 2021

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

ROMŽOVÁ, Marianna, Dagmar SMITALOVÁ, Jakub HYNŠT, Nikola TOM, Tomáš LOJA et. al.

Basic information

Original name

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

Authors

ROMŽOVÁ, Marianna (703 Slovakia, guarantor, belonging to the institution), Dagmar SMITALOVÁ (203 Czech Republic, belonging to the institution), Jakub HYNŠT (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Tomáš LOJA (703 Slovakia, belonging to the institution), Zdeňka HERUDKOVÁ (203 Czech Republic, belonging to the institution), Tomáš JURČEK (203 Czech Republic), Lukas STEJSKAL (203 Czech Republic), Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Zdeněk RÁČIL (203 Czech Republic) and Martin ČULEN (703 Slovakia, belonging to the institution)

Edition

British journal of haematology, Hoboken, Wiley-Blackwell, 2021, 0007-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.615

RIV identification code

RIV/00216224:14740/21:00120115

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1111/bjh.17659

UT WoS

000668741700001

Keywords in English

CML; NGS; progenitors; leukaemic stem cells; somatic mutations; ASXL1

Abstract

V originále

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.

Links

MUNI/A/1595/2020, interní kód MU

Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VIII (Acronym: VýDiTeHeMa VIII)

Investor: Masaryk University

NV17-30397A, research and development project

Name: Mutační analýza primitivních buněčných populací u chronické myeloidní leukémie: za hranicí BCR-ABL1

90132, large research infrastructures

Name: NCMG II

Citovat

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. 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.

@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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