High-Density Screening Reveals a Different Spectrum of Genomic Aberrations in Chronic Lymphocytic Leukemia Patients with "stereotyped" IGHV3-21 and IGHV4-34 B-Cell Receptors

Millaray Marincevic, Uppsala Universitet
Nicola Cahill, Uppsala Universitet
Rebeqa Gunnarsson, Lund University
Anders Isaksson, Uppsala Universitet
Mahmoud Mansouri, Uppsala Universitet
Mattias Jansson, Uppsala Universitet
Fergus Ryan, Technological University Dublin
Karin Karlsson, Lund University
Hans-Olov Adami, Karolinska Institute
Fred Davi, Universite Pierre et Marie Curie (Paris VI)
Jesper Jurlander, Rigshospitalet, Copenhagen
Gunnar Juliousson, Lund University
Kostas Stamatopoulos, Papanicolaou Hospital, Thessaloniki
Richard Rosenquist, Uppsala Universitet

Document Type Article

Haematologica 2010, 95, 9, pp1519-1525


The existence of multiple subsets of chronic lymphocytic leukemia expressing ‘stereotyped’ Bcell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that ‘stereotypy’ may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors;
however, little is known regarding the genomic profile of patients in these subsets.
Design and Methods
We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients.
Over 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to
patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and nonsubset
#4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy.
Genomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently
low-proliferative disease, which would prevent accumulation of genomic alterations.