Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00076479" target="_blank" >RIV/65269705:_____/22:00076479 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/22:00127827
Result on the web
<a href="https://www.tandfonline.com/doi/epdf/10.1080/15592294.2022.2050004?needAccess=true&role=button" target="_blank" >https://www.tandfonline.com/doi/epdf/10.1080/15592294.2022.2050004?needAccess=true&role=button</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/15592294.2022.2050004" target="_blank" >10.1080/15592294.2022.2050004</a>
Alternative languages
Result language
angličtina
Original language name
Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene
Original language description
Genome methylation profiles define naive-like (n-CLL), memory-like (m-CLL), and intermediate (i-CLL) subsets of chronic lymphocytic leukaemia (CLL). The profiles can be easily determined by the analysis of the five-CpG signature. m-CLL, i-CLL, and n-CLL with the good, intermediate, and poor prognoses, respectively, differ by the somatic hypermutation status of the immunoglobulin heavy chain variable gene (IGHV), a widely used prognostic predictor in CLL. We have previously shown that the expression of WNT5A, encoding a ROR1 ligand, distinguishes patients with the worse outcome within the prognostically favourable IGHV-mutated subgroup. To analyse the mechanisms controlling WNT5A expression, we investigated the methylation status of 54 CpG sites within the WNT5A promoter and its relation to the WNT5A gene expression. In a cohort of 59 CLL patients balanced for combinations of IGHV and WNT5A statuses, we identified three promoter CpG sites whose methylation level correlated with the WNT5A expression within the IGHV-mutated subgroup. Further, we complemented our data with the methylation status of the five-CpG signature. IGHV-mutated/WNT5A-negative and IGHV-mutated/WNT5A-positive cases overlapped with m-CLL and i-CLL methylation subgroups, respectively, while most IGHV-unmutated samples were assigned to n-CLL. Median methylation levels of all the three CpG sites in the WNT5A promoter were lowest in i-CLL. Finally, a detailed analysis of m-CLL and i-CLL showed that undetectable WNT5A expression predicts longer treatment-free survival with higher statistical significance than the classification according to the five-CpG signature. To conclude, a favourable m-CLL subgroup is associated with mutated IGHV and undetectable WNT5A expression due to its promoter methylation.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Epigenetics
ISSN
1559-2294
e-ISSN
1559-2308
Volume of the periodical
17
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
1628-1635
UT code for WoS article
000780374400001
EID of the result in the Scopus database
2-s2.0-85127231282