Journal
BLOOD
Volume 119, Issue 19, Pages 4467-4475Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-11-393694
Keywords
-
Categories
Funding
- ENosAI [09SYN-13-880]
- European Union
- Hellenic General Secretariat for Research and Technology
- Cariplo Foundation, Milan, Italy
- Program Molecular Clinical Oncology-5 per mille [9965]
- Associazione Italiana per la Ricerca sul Cancro (AIRC), Milano, Italy
- National Cancer Institute/National Institutes of Health [RO1 CA81554]
- Nordic Cancer Union
- Swedish Cancer Society
- Swedish Research Council
- Uppsala University Hospital
- Lion's Cancer Research Foundations in Uppsala
- Ministry of Health of the Czech Republic [MZ CZ NS10439-3/2009]
- A. G. Leventis Foundation
Ask authors/readers for more resources
Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of CLL-biased features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1: 2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset. (Blood. 2012;119(19):4467-4475)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available