RT Journal Article
T1 TRAF3 alterations are frequent in del‐3′IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features
A1 Pérez Carretero, Claudia
A1 Hernández Rivas, José Ángel
A1 Hernández Sánchez, María
A1 González, Teresa
A1 Quijada Álamo, Miguel
A1 Martín Izquierdo, Marta
A1 Santos Mínguez, Sandra
A1 Miguel García, Cristina
A1 Vidal, María Jesús
A1 García de Coca, Alfonso
A1 Galende, Josefina
A1 Pardal, Emilia
A1 Aguilar, Carlos
A1 Vargas Pabón, Manuel
A1 Dávila, Julio
A1 Gascón y Marín, Isabel
A1 Hernández Rivas, José Ángel
A1 Benito, Rocío
A1 Rodríguez Vicente, Ana Eugenia
AB Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 30 IGH (del-30 IGH CLLs), which  contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-30IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-30 IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-30 IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-30 IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor forTFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-30 IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.
PB Wiley
SN 0361-8609
SN 1096-8652
YR 2022
FD 2022-05-09
LK https://hdl.handle.net/20.500.14352/110926
UL https://hdl.handle.net/20.500.14352/110926
LA eng
NO Pérez‐Carretero, Claudia, et al. «TRAF3 Alterations Are Frequent in Del‐3′ IGH Chronic Lymphocytic Leukemia Patients and Define a Specific Subgroup with Adverse Clinical Features». American Journal of Hematology, vol. 97, n.o 7, julio de 2022, pp. 903-14. DOI.org (Crossref), https://doi.org/10.1002/ajh.26578.
NO Fondo de Investigacines Sanitarias (España)
NO Instituto de Salud Carlos III
NO European Commission-ERC
NO Consejería de Educacion, Junta de Castilla y Leon
NO Gerencia Regional de Salud
NO Fundacion Memoria Don Samuel Solorzano Barruso
NO Red Temática de Investigacion Cooperativa en Cáncer
NO Centro de Investigacion Biomédica en Red de Cáncer
DS Docta Complutense
RD 21 ene 2026