Abstract
Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P < 1 × 10(-4) ) and CD38 (P < 1 × 10(-4) ) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion.
Highlights
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease having an indolent course in most patients who may survive for many years without treatment, or showing an aggressive and rapidly progressive outcome in others [1,2]
We investigated the occurrence of 2p gain in a series of newly diagnosed, untreated CLL cases included in the research article
Previous retrospective studies based on fluorescence in situ hybridization (FISH), comparative genomic hybridization and single nucleotide polymorphism (SNP) array identified
Summary
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease having an indolent course in most patients who may survive for many years without treatment, or showing an aggressive and rapidly progressive outcome in others [1,2]. A number of cellular and molecular markers help to classify CLL into biologically and clinically distinct subgroups, and to predict the clinical course of the disease at diagnosis [5]. CLL patients with unmutated (UM) immunoglobulin heavy chain variable (IGHV) region genes (>98% homology to germline sequences), increased expression of the CD38 cell surface antigen, or increased expression of the. 70-kd zeta-chain T-cell receptor–associated protein kinase (ZAP-70) experience a shorter therapy-free interval, and a more aggressive behavior [6,7,8]. Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano e Ematologia 1 CTMO, Fondazione IRCCS Ca’ Granda Ospedale Maggiore
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