TY  - JOUR
AU  - Cabrera-Serrano, Antonio José
AU  - Sánchez-Maldonado, José Manuel
AU  - Rodríguez-Sevilla, Juan José
AU  - Reyes-Zurita, Fernando Jesús
AU  - Collado, Rosa
AU  - Puiggros, Anna
AU  - Cornejo-Calvo, Elena
AU  - García, Paloma
AU  - Ter Horst, Rob
AU  - Benavente, Yolanda
AU  - Jerez, Andrés
AU  - Landi, Stefano
AU  - Espinet, Blanca
AU  - Maffei, Rossana
AU  - López-Nevot, Miguel Ángel
AU  - Ramos-Campoy, Silvia
AU  - González-Olmedo, Carmen
AU  - Chen-Liang, Tzu-Hua
AU  - Moreno, Victor
AU  - Jannus, Fatin
AU  - Marcos-Gragera, Rafael
AU  - Carretero-Fernández, María
AU  - Sampaio-Marques, Belém
AU  - Gámez, Irene
AU  - Garcia-Alvarez, María
AU  - Camp, Nicola J
AU  - Dierssen-Sotos, Trinidad
AU  - Kamaso, Joanna
AU  - Pérez, Eva María
AU  - Norman, Aaron D
AU  - Luppi, Mario
AU  - Li, Yang
AU  - Alcoceba, Miguel
AU  - Campa, Daniele
AU  - de Sanjose, Silvia
AU  - Marasca, Roberto
AU  - Ludovico, Paula
AU  - Clay-Gilmour, Alyssa Ione
AU  - Canzian, Federico
AU  - Ibañez, Marian
AU  - Netea, Mihai G
AU  - McKay, James
AU  - Casabonne, Delphine
AU  - Berndt, Sonja I
AU  - Slager, Susan L
AU  - Sainz, Juan
TI  - Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.
JO  - Blood advances
VL  - nn
SN  - 2473-9529
CY  - Washington, DC
PB  - American Society of Hematology
M1  - DKFZ-2025-01837
SP  - nn
PY  - 2025
N1  - epub
AB  - We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.57×10⁻¹²). We also validated previously reported associations for FAS, BCL2, and BAK1 SNPs with CLL risk (p=4.73×10⁻²¹ to 3.39×10⁻⁹). The CDKN2Ars3731204 and FASrs1926194 SNPs associated with increased CDKN2A and ACTA2 mRNA expression levels in whole blood and/or lymphocytes (p=5.1×10-7, p=1.58×10-21, and p=7.8×10-41), although no significant effect on autophagy flux was observed. However, associations were found between CDKN2A, BCL2, and FAS SNPs and various T-cell subsets, cytokine production, and circulating concentrations of IFNg, TRAIL, CD40, CCL20, and IL2RB proteins (p≤0.005). No significant association was detected between autophagy variants and OS or TTFT, suggesting that these variants drive disease initiation rather than progression. In conclusion, this study identified four novel associations for CLL and provided insights into the biological pathways that influence CLL development.
LB  - PUB:(DE-HGF)16
C6  - pmid:40902075
DO  - DOI:10.1182/bloodadvances.2025017345
UR  - https://inrepo02.dkfz.de/record/304302
ER  -