Comprehensive characterization of IGHV3-21–expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study

Abstract

IGHV3-21-using chronic lymphocytic leukemia (CLL) is a distinct entity

Are surrogates of IGHV gene mutational status useful in B-cell chronic lymphocytic leukemia? The example of Septin-10

“…[3][4][5] Consistently, GEP studies performed by our group and comparison of IGHV3-21 CLL versus non-IGHV3-21 CLL have identified a restricted number of genes (122 probes corresponding to 115 genes) whose differential expression may explain, at least in part, the clinical aggressiveness of IGHV3-21 CLL. 3 By reviewing the list of the 122 probes differentially expressed by IGHV3-21 CLL, 1 we found SEPT10 among the 62 probes (59 genes) significantly downregulated in this CLL subset. 3 Downregulation of SEPT10 in IGHV3-21 CLL was an unexpected finding, because SEPT10 expression is considered a poor prognostic marker and IGHV3-21 CLL typically has poor clinical outcome.…”

“…1 We recently reported a comprehensive characterization of IGHV3-21-expressing CLL, a disease subset recognized as a specific poor prognosis category, given its clinical behavior mostly independent of IGHV gene mutation status. 3 In this respect, we and others have demonstrated that IGHV3-21 CLL, although frequently displaying a mutated (M) IGHV gene configuration, has an overall survival similar to poor-prognosis UM CLL. [3][4][5] Consistently, GEP studies performed by our group and comparison of IGHV3-21 CLL versus non-IGHV3-21 CLL have identified a restricted number of genes (122 probes corresponding to 115 genes) whose differential expression may explain, at least in part, the clinical aggressiveness of IGHV3-21 CLL.…”

“…3 In this respect, we and others have demonstrated that IGHV3-21 CLL, although frequently displaying a mutated (M) IGHV gene configuration, has an overall survival similar to poor-prognosis UM CLL. [3][4][5] Consistently, GEP studies performed by our group and comparison of IGHV3-21 CLL versus non-IGHV3-21 CLL have identified a restricted number of genes (122 probes corresponding to 115 genes) whose differential expression may explain, at least in part, the clinical aggressiveness of IGHV3-21 CLL. 3 By reviewing the list of the 122 probes differentially expressed by IGHV3-21 CLL, 1 we found SEPT10 among the 62 probes (59 genes) significantly downregulated in this CLL subset.…”

“…3 By reviewing the list of the 122 probes differentially expressed by IGHV3-21 CLL, 1 we found SEPT10 among the 62 probes (59 genes) significantly downregulated in this CLL subset. 3 Downregulation of SEPT10 in IGHV3-21 CLL was an unexpected finding, because SEPT10 expression is considered a poor prognostic marker and IGHV3-21 CLL typically has poor clinical outcome.…”

“…Bioinformatic analyses were performed by applying the same multi-significance analysis of microarrays (multi-SAM) approach that has been previously employed and that was purposely set up to deal with unbalanced data sets (11 versus 29 samples). 3 This approach consists in a recursive application of SAM so that the lesspopulated UM/CD38 high CLL class (11 cases) was compared with a series of random samplings (1000 samplings), each of them of 11 cases, from the more-populated M/CD38 low CLL class. For each single application of SAM, a list of differentially expressed genes (that is, with adjusted Po10 À3 ) was generated.…”