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@article{2245078,
author = {Poppová, Lucie and Pavlová, Šárka and Gonzalez, Beatriz and Kotašková, Jana and Plevová, Karla and Dumbovic, Gabrijela and Janovská, Pavlína and Bystrý, Vojtěch and Panovská, Anna and Bezděková, Lucie and Mašlejová, Stanislava and Brychtová, Yvona and Doubek, Michael and Krzyžánková, Marcela and Borský, Marek and Mayer, Jiří and Bryja, Vítězslav and Alonso, Sergio and Pospíšilová, Šárka},
article_location = {Philadelphia},
article_number = {12},
doi = {http://dx.doi.org/10.1080/15592294.2022.2050004},
keywords = {WNT5A; chronic lymphocytic leukaemia; methylation; i-CLL; m-CLL},
language = {eng},
issn = {1559-2294},
journal = {Epigenetics},
title = {Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene},
url = {https://www.tandfonline.com/doi/full/10.1080/15592294.2022.2050004},
volume = {17},
year = {2022}
}
TY - JOUR
ID - 2245078
AU - Poppová, Lucie - Pavlová, Šárka - Gonzalez, Beatriz - Kotašková, Jana - Plevová, Karla - Dumbovic, Gabrijela - Janovská, Pavlína - Bystrý, Vojtěch - Panovská, Anna - Bezděková, Lucie - Mašlejová, Stanislava - Brychtová, Yvona - Doubek, Michael - Krzyžánková, Marcela - Borský, Marek - Mayer, Jiří - Bryja, Vítězslav - Alonso, Sergio - Pospíšilová, Šárka
PY - 2022
TI - Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene
JF - Epigenetics
VL - 17
IS - 12
SP - 1628-1635
EP - 1628-1635
PB - TAYLOR & FRANCIS INC
SN - 15592294
KW - WNT5A
KW - chronic lymphocytic leukaemia
KW - methylation
KW - i-CLL
KW - m-CLL
UR - https://www.tandfonline.com/doi/full/10.1080/15592294.2022.2050004
N2 - 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.
ER -
POPPOVÁ, Lucie, Šárka PAVLOVÁ, Beatriz GONZALEZ, Jana KOTAŠKOVÁ, Karla PLEVOVÁ, Gabrijela DUMBOVIC, Pavlína JANOVSKÁ, Vojtěch BYSTRÝ, Anna PANOVSKÁ, Lucie BEZDĚKOVÁ, Stanislava MAŠLEJOVÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Marcela KRZYŽÁNKOVÁ, Marek BORSKÝ, Jiří MAYER, Vítězslav BRYJA, Sergio ALONSO and Šárka POSPÍŠILOVÁ. Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene. \textit{Epigenetics}. Philadelphia: TAYLOR \&{} FRANCIS INC, 2022, vol.~17, No~12, p.~1628-1635. ISSN~1559-2294. Available from: https://dx.doi.org/10.1080/15592294.2022.2050004.
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