- Millaray Marincevic1,
- Nicola Cahill1,
- Rebeqa Gunnarsson2,
- Anders Isaksson1,
- Mahmoud Mansouri1,
- Hanna Göransson1,
- Markus Rasmusson1,
- Mattias Jansson1,
- Fergus Ryan3,
- Karin Karlsson2,
- Hans-Olov Adami4,
- Fred Davi5,
- Jesper Jurlander6,
- Gunnar Juliusson2,
- Kostas Stamatopoulus7 and
- Richard Rosenquist1,*
- 1 Uppsala University, Sweden;
- 2 Lund University, Sweden;
- 3 Dublin Institute of Technology, Ireland;
- 4 Karolinska Institutet, Sweden;
- 5 Hôpital Pitié-Salpêtrière et Université Pierre et Marie Curie, France;
- 6 Rigshospitalet, Denmark;
- 7 G. Papanicolaou Hospital, Greece
- ↵* Corresponding author; email:
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.
- Received December 9, 2009.
- Accepted March 18, 2010.
- Copyright © 2010, Ferrata Storti Foundation