RT Journal Article
SR Electronic
T1 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
JF Haematologica
JO Haematologica
FD Ferrata Storti Foundation
SP haematol.2009.021014
DO 10.3324/haematol.2009.021014
A1 Marincevic, Millaray
A1 Cahill, Nicola
A1 Gunnarsson, Rebeqa
A1 Isaksson, Anders
A1 Mansouri, Mahmoud
A1 GĂ¶ransson, Hanna
A1 Rasmusson, Markus
A1 Jansson, Mattias
A1 Ryan, Fergus
A1 Karlsson, Karin
A1 Adami, Hans-Olov
A1 Davi, Fred
A1 Jurlander, Jesper
A1 Juliusson, Gunnar
A1 Stamatopoulus, Kostas
A1 Rosenquist, Richard
YR 2010
UL http://www.haematologica.org/content/early/2010/04/26/haematol.2009.021014.abstract
AB Background. The existence of multiple subsets of chronic lymphocytic leukemia (CLL) cases expressing 'stereotyped' B-cell receptors (BCRs) implies involvement of antigen(s) in leukemogenesis. Studies also indicate that 'stereotypy' may influence clinical course in CLL, e.g. in subsets with stereotyped IGHV3-21 and IGHV4-34 BCRs; however, little is known regarding their genomic profile. Design and Methods. We applied 250K SNP-arrays to study copy-number aberrations (CNAs) and copy-number neutral loss-of-heterozygosity (CNN-LOH) in 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. Results. Over 90% of subset #2 and non-subset #2 carried CNAs, whereas 75-76% of subset #4 and subset #16 showed CNAs. Subset #2 and non-subset #2 also displayed a higher average number of aberrations compared to subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%), however, this aberration was even more frequent in subset #2 (79%). Furthermore, del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) relative to subset #4 and non-subset #4/16 patients. Recurrent CNN-LOH was mainly detected on chromosome 13q, independent of BCR stereotypy. Conclusions. Genomic aberrations were more common in subset #2 and non-subset #2 compared to subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for these patients. Conversely, the lower prevalence of CNAs and the absence of poor-prognostic aberrations in subset #4 may reflect an inherent low-proliferative disease, thus preventing accumulation of genomic alterations.