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Clonal hierarchy of main molecular lesions in acute myeloid leukaemia

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00115741" target="_blank" >RIV/00216224:14110/20:00115741 - isvavai.cz</a>

  • Alternative codes found

    RIV/65269705:_____/20:00072323

  • Result on the web

    <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16341" target="_blank" >https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16341</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1111/bjh.16341" target="_blank" >10.1111/bjh.16341</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Clonal hierarchy of main molecular lesions in acute myeloid leukaemia

  • Original language description

    Genetic mutations in acute myeloid leukaemia (AML) are assumed to occur in a sequential order; however, the predominant hierarchical roles of specific mutated genes have not been fully described. In this study, we aimed to determine the clonal involvement of the most frequent AML-associated mutations. Using a targeted sequencing panel for 18 genes, we traced changes and relative clonal contribution of mutations in 52 patients. We analysed 35 pairs of diagnosis and relapse samples, 27 pairs of primary samples and corresponding patient-derived xenografts, and 34 pairs of total leukocytes and corresponding isolated primitive cells or blast populations. In both relapse and xenografts, we observed conservation of main leukaemic clones and variability was limited to subclones with late-acquired mutations. AML evolution thus mainly involved modification of subclones while the clonal background remained unchanged. NPM1 mutations were identified as the most probable leukaemia-transformation lesion, remaining conserved in contrast to high variation of accompanying subclonal FLT3 and NRAS mutations. DNMT3A mutations represented the most stable mutations forming a preleukaemic background in most samples. Mutations in genes IDH1/2, TET2, RUNX1, ASXL1 and U2AF1 were detected both as preleukaemic and as subclonal lesions, suggesting a non-specific order of acquisition.

  • 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

    <a href="/en/project/NV15-25809A" target="_blank" >NV15-25809A: National study of leukemia cell mutations and clonality in patients diagnosed with acute myeloid leukemia</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Others

  • Publication year

    2020

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    British journal of haematology

  • ISSN

    0007-1048

  • e-ISSN

    1365-2141

  • Volume of the periodical

    190

  • Issue of the periodical within the volume

    4

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    11

  • Pages from-to

    562-572

  • UT code for WoS article

    000501700400001

  • EID of the result in the Scopus database

    2-s2.0-85076350465