Relevance of Chromosome 2p Gain in Early Binet Stage A Chronic Lymphocytic Leukemia (expression)

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by chromosomal aberrations of prognostic significance. Recent studies showed that gain of chromosome 2p is a recurrent lesion in CLL. We investigated the 2p gain and its relationship with prognostic biomarkers in a prospective series of 287 early-stage CLLs (Binet A). The 2p gain was detected by FISH in 17 patients (6%) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e. del(11)(q23) and del(17)(p13) (P=0.002) as well as unmutated (UM) status of IGHV (P<110-4) and CD38 (P<110-4) and ZAP-70 positive expression (P=0.003) were significantly more prevalent in 2p gain cases. Furthermore, 2p gained patients showed a significantly higher occurrence of stereotyped HCDR3 sequences compared to 2p normal CLLs (P=0.009). Among the stereotyped subsets, the incidence of subset #1 in 2p positive patients was significantly higher than that found in the remaining CLLs (P=0.031). Finally, gene expression profiling analysis identified a number of genes significantly upregulated in 2p gain CLLs. Among those located at 2p, 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. Our study indicates that 2p gain is a recurrent lesion in early CLL, correlated with the major biological and cytogenetic risk markers of the disease. Moreover, we provide insights to define novel candidate genes that may play additional pathogenetic roles in CLL.

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Fabris S, Mosca L, Cutrona G, Lionetti M, Agnelli L, Ciceri G, Barbieri M, Maura F, Matis S, Colombo M, Gentile M, Recchia AG, Anna Pesce E, Di Raimondo F, Musolino C, Gobbi M, Di Renzo N, Mauro FR, Brugiatelli M, Ilariucci F, Lipari MG, Angrilli F, Consoli U, Fragasso A, Molica S, Festini G, Vincelli I, Cortelezzi A, Federico M, Morabito F, Ferrarini M, Neri A