Memory B-cell like chronic lymphocytic leukaemia is associated
with specific methylation profile of WNT5A promoter and
undetectable expression of WNT5A gene

J 2022

Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene

POPPOVÁ, Lucie, Šárka PAVLOVÁ, Beatriz GONZALEZ, Jana KOTAŠKOVÁ, Karla PLEVOVÁ et. al.

Basic information

Original name

Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile of WNT5A promoter and undetectable expression of WNT5A gene

Authors

POPPOVÁ, Lucie (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Beatriz GONZALEZ, Jana KOTAŠKOVÁ (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Gabrijela DUMBOVIC, Pavlína JANOVSKÁ (203 Czech Republic, belonging to the institution), Vojtěch BYSTRÝ (203 Czech Republic, belonging to the institution), Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Lucie BEZDĚKOVÁ (203 Czech Republic, belonging to the institution), Stanislava MAŠLEJOVÁ (703 Slovakia, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Marcela KRZYŽÁNKOVÁ (203 Czech Republic, belonging to the institution), Marek BORSKÝ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Vítězslav BRYJA (203 Czech Republic, belonging to the institution), Sergio ALONSO and Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Epigenetics, Philadelphia, TAYLOR & FRANCIS INC, 2022, 1559-2294

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: 3.700

RIV identification code

RIV/00216224:14110/22:00127827

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1080/15592294.2022.2050004

UT WoS

000780374400001

Keywords in English

WNT5A; chronic lymphocytic leukaemia; methylation; i-CLL; m-CLL

Abstract

V originále

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.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

LM2018133, research and development project

Name: Český národní uzel Evropské infrastruktury pro translační medicínu (Acronym: EATRIS-ERIC-CZ)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1330/2021, interní kód MU

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

Investor: Masaryk University

90133, large research infrastructures

Name: EATRIS-CZ III

Citovat

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. 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.

@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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