Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis

Kolijn, P. Martijn ; Hosnijeh, Fatemeh Saberi ; Späth, Florentin ; Hengeveld, Paul J. ; Agathangelidis, Andreas ; Saleh, Manal ; Casabonne, Delphine ; Benavente, Yolanda ; Jerkeman, Mats LU and Agudo, Antonio , et al. (2022) In Blood 139(10). p.1557-1563
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
139
issue
10
pages
7 pages
publisher
American Society of Hematology
external identifiers
  • pmid:34662377
  • scopus:85122045401
ISSN
0006-4971
DOI
10.1182/blood.2021012890
language
English
LU publication?
yes
id
6cb41925-1539-4831-a356-513711367d04
date added to LUP
2023-01-16 10:05:27
date last changed
2024-05-30 00:34:28
@article{6cb41925-1539-4831-a356-513711367d04,
  abstract     = {{<p>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.</p>}},
  author       = {{Kolijn, P. Martijn and Hosnijeh, Fatemeh Saberi and Späth, Florentin and Hengeveld, Paul J. and Agathangelidis, Andreas and Saleh, Manal and Casabonne, Delphine and Benavente, Yolanda and Jerkeman, Mats and Agudo, Antonio and Barricarte, Aurelio and Besson, Caroline and Sánchez, Maria Jose and Chirlaque, María Dolores and Masala, Giovanna and Sacerdote, Carlotta and Grioni, Sara and Schulze, Matthias B. and Nieters, Alexandra and Engelfriet, Peter and Hultdin, Magnus and McKay, James D. and Vermeulen, Roel C.H. and Langerak, Anton W.}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{10}},
  pages        = {{1557--1563}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis}},
  url          = {{http://dx.doi.org/10.1182/blood.2021012890}},
  doi          = {{10.1182/blood.2021012890}},
  volume       = {{139}},
  year         = {{2022}},
}