Data from Expression of Mutated &lt;i&gt;IGHV3-23&lt;/i&gt; Genes in Chronic Lymphocytic Leukemia Identifies a Disease Subset with Peculiar Clinical and Biological Features

Rossana Maffei,Pietro Bulian,Massimo Degan,Antonella Zucchetto,Francesco Bertoni,Milena S Nicoloso,Davide Rossi,Elisa Sozzi,Ilaria Cattarossi,Daniela Marconi,Francesca Maria Rossi,Valter Gattei,Dimitar G Efremov,Maria Ilaria Del Principe,Emanuele Zucca,Dania Benedetti,Roberto Marasca,Francesco Forconi,Riccardo Bomben,Daniela Capello,Fabrizio Luciano,Giovanni Del Poeta,Luca Laurenti,Gianluca Gaïdano ,Michele Dal Bo

doi:10.1158/1078-0432.c.6517659

Abstract

<div>AbstractPurpose: B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease whose outcome can be foreseen by investigating the mutational status of immunoglobulin heavy chain variable (IGHV) genes. Moreover, a different prognosis was reported for CLL expressing specific IGHV genes in the context or not of stereotyped B-cell receptors. Here we investigated novel associations between usage of specific IGHV genes and clinical features in CLL.Experimental Design: Among 1,426 CLL-specific IG-rearrangements, stereotyped B-cell receptor clusters never utilized the IGHV3-23 gene. Given this notion, this study was aimed at characterizing the IGHV3-23 gene in CLL, and identifying the properties of IGHV3-23–expressing CLL.Results: IGHV3-23 was the second most frequently used (134 of 1,426) and usually mutated (M; 109 of 134) IGHV gene in our CLL series. In the vast majority of M IGHV3-23 sequences, the configuration of the 13 amino acids involved in superantigen recognition was consistent with superantigen binding. Clinically, M IGHV3-23 CLL had shorter time-to-treatment than other M non–IGHV3-23 CLL, and multivariate analyses selected IGHV3-23 gene usage, Rai staging, and chromosomal abnormalities as independent prognosticators for M CLL. Compared with M non–IGHV3-23 CLL, the gene expression profile of M IGHV3-23 CLL was deprived in genes, including the growth/tumor suppressor genes PDCD4, TIA1, and RASSF5, whose downregulation is under control of miR-15a and miR-16-1. Accordingly, relatively higher levels of miR-15a and miR-16-1 were found in M IGHV3-23 compared with M non–IGHV3-23 CLL.Conclusions: Altogether, expression of the IGHV3-23 gene characterizes a CLL subset with distinct clinical and biological features. Clin Cancer Res; 16(2); 620–8</div>

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