Stereotyped subset #1 chronic lymphocytic leukemia: a direct link between B‐cell receptor structure, function, and patients' prognosis. Issue 1 (15th November 2013)

• Record Type: Journal Article
• Authors: Del, Ilaria; Chiaretti, Sabina; Santangelo, Simona; Tavolaro, Simona; Peragine, Nadia; Marinelli, Marilisa; Ilari, Caterina; Raponi, Sara; Messina, Monica; Nanni, Mauro; Mauro, Francesca Romana; Piciocchi, Alfonso; Bontempi, Katia; Rossi, Davide; Gaidano, Gianluca; Guarini, Anna; Foà, Robin
• Is Part Of: American journal of hematology. Volume 89:Issue 1(2014:Jan.)
• Page Start: 74
• Page End: 82
• Publication Date: 2013-11-15
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23591
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Chronic lymphocytic leukemia (CLL) with stereotyped B‐cell receptor (BCR) belonging to subset #1 (IGHV1‐5‐7/IGKV1‐39) display a poor outcome. To characterize their genetic and genomic features and BCR function, we selected 20 subset #1 CLL from a series of 579 cases. Subset #1 CLL, all showing unmutated IGHV, were associated with the presence of del(11q) (50%) in comparison with unmutated CLL, unmutated stereotyped CLL other than subset #1 and with cases using the same IGHV genes but a heterogeneous VH CDR3 (non‐subset #1 CLL). There were no distinctive features regarding CD38, ZAP‐70, and <italic>TP53</italic> disruption. <italic>NOTCH1</italic>, <italic>SF3B1</italic>, and <italic>BIRC3</italic> were mutated in 15%, 0%, and 5% of cases, respectively, while <italic>BIRC3</italic> was deleted in 22% of cases. Microarray unsupervised analysis on 80 unmutated/mutated/stereotyped/non‐stereotyped CLL showed a tight clustering of subset #1 cases. Their genomic signature exhibited several differentially expressed transcripts involved in BCR signal transduction, apoptosis regulation, cell proliferation, and oxidative processes, regardless of del(11q). Accordingly, BCR ligation with anti‐IgM revealed a significant higher proliferation of subset #1 versus unmutated non‐subset #1 CLL, both at baseline and after 24–48 hr stimulation. Subset #1 CLL represent a paradigmatic example of the direct link between BCR structure, function, and patients prognosis. Am. J. Hematol. 89:74–82, 2014. © 2013 Wiley Periodicals, Inc.</p> </abstract>