RT Journal Article
T1 High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis.
A1 Kolijn, P Martijn
A1 Hosnijeh, Fatemeh Saberi
A1 Späth, Florentin
A1 Hengeveld, Paul J
A1 Agathangelidis, Andreas
A1 Saleh, Manal
A1 Casabonne, Delphine
A1 Benavente, Yolanda
A1 Jerkeman, Mats
A1 Agudo, Antonio
A1 Barricarte, Aurelio
A1 Besson, Caroline
A1 Sanchez-Perez, Maria-Jose
A1 Chirlaque, María-Dolores
A1 Masala, Giovanna
A1 Sacerdote, Carlotta
A1 Grioni, Sara
A1 Schulze, Matthias B
A1 Nieters, Alexandra
A1 Engelfriet, Peter
A1 Hultdin, Magnus
A1 McKay, James D
A1 Vermeulen, Roel C H
A1 Langerak, Anton W
AB Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.
PB American Society of Hematology
YR 2022
FD 2022
LK http://hdl.handle.net/10668/20244
UL http://hdl.handle.net/10668/20244
LA en
NO Kolijn PM, Hosnijeh FS, Späth F, Hengeveld PJ, Agathangelidis A, Saleh M, et al. AW. High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis. Blood. 2022 Mar 10;139(10):1557-1563.
DS RISalud
RD Apr 4, 2025