Published online 26 April 2010
(Haematologica 2010, 10.3324/haematol.2009.021014)
Copyright © 2010 by Ferrata Storti Foundation
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Chronic Lymphocytic Leukemia

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 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, 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: richard.rosenquist{at}genpat.uu.se

ABSTRACT

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.

Key words: Chronic Lymphocytic Leukemia, 'Stereotyped' subsets, High density genomic arrays, IGHV3-21, IGHV4-34.


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Thorsten Zenz, Daniel Mertens, Stephan Stilgenbauer
Haematologica 2010 95: 1441-1443. [Full Text] [PDF]



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T. Zenz, D. Mertens, and S. Stilgenbauer
Biological diversity and risk-adapted treatment of chronic lymphocytic leukemia
Haematologica, September 1, 2010; 95(9): 1441 - 1443.
[Full Text] [PDF]