Frequency of 5′IGH deletions in B-cell chronic lymphocytic leukemia

In a retrospective analysis of a large group of cases (n = 291) with B-cell CLL diagnosis, the various characteristics of IGH aberrations as identified by fluorescence in situ hybridization (FISH) probes were studied. Conventional cytogenetic and FISH studies with the standard panel (13q14, 11q13, 17p13, 12 centromere), and with IGH break-apart probes were done for each case. Abnormal karyotypes were detected with conventional cytogenetics in 29% of cases, and FISH detected abnormalities in 70%. Deletion of 13q14 was the most frequent anomaly, followed by trisomy 12, deletion of 11q, and deletion of 17 p. Among the IGH abnormalities detected, translocations with unknown partners (split signals) occurred in only a small group of patients (15%). Instead, deletion of 5′IGH, corresponding to the variable IGH segment (IGHV) was the most recurrent aberration, observed in 82% (the second most common finding among our patients). This deletion was associated with good prognostic markers: 13q14 deletion, normal karyotype, and CD38 and ZAP-70 negative expression. Although not exclusive to CLL, the deletion occurred in a high frequency, in contrast to its rarity in other B-cell lymphoproliferative disorders. Longitudinal studies are warranted, to determine when in the disease progression this abnormality is acquired, as a potential early marker, and its impact on the natural history of CLL.