TRAF3 alterations are frequent in del‐3′ <scp>IGH</scp> chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features

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 3′IGH (del-3′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-3′IGH 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-3′IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3′IGH CLLs than in the control group (p
Funding information: Universidad de Salamanca; Fundación Española de Hematología y Hemoterapia (FEHH); Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Grant/Award Number: CB16/12/00233; Red Temática de Investigación Cooperativa en Cáncer (RTICC); “Fundación Memoria Don Samuel Solórzano Barruso”: FS/33–2020, Grant/Award Number: RD12/0036/0069; “Gerencia Regional de Salud, SACYL”:, Grant/Award Numbers: GRS2385/A/21, GRS2140/A/20; Consejería de Educación, Junta de Castilla y León, Grant/Award Number: SA118P20; European Regional Development Fund and Instituto de Salud Carlos III, Grant/Award Numbers: CD19/00222, FI19/00191; Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI21/00983, PI18/01500