Background: Genetic analysis has an important role in the diagnosis, classification, and management of patients with CLL. Although translocations involving the IGH locus are well characterized in B-cell malignancies such as follicular cell lymphoma, their frequency in CLL are less well defined and little is known about their prognostic significance. We studied a series of CLL patients using a FISH probe set which included an IGH probe and reviewed clinical data and disease course of CLL patients with IGH translocations.

Methods: FISH was performed on blood using a DNA probe set designed to detect common chromosome anomalies associated with CLL and translocations involving IGH. Patients with an IGH abnormality were further studied using FISH probes sets for IGH and cyclin D1, BCL-2, BCL-3, BCL-6, BCL-11a, c-MYC, MALT-1, c-MAF, FGFR-3 or PAX-5. Between 5/15/03 and 5/15/07, samples from 4,976 patients with a presumed lymphoproliferative disorder were analyzed by FISH. Of these, 316 patients (6.3%) had translocations involving the IGH locus. Sixty-three (21%) of the 316 patients with IGH translocations had been seen at Mayo Clinic Rochester and had clinical and laboratory data for detailed review and analysis of associations to the FISH results.

Results: We identified 39 patients with CLL and IGH translocations. Identified partner genes were: BCL-2 (n=22), BCL-3 (n=7), CMYC (n=2), MALT-1 (n=1). The partner gene was not identified despite using above mentioned panel of partner gene probes in 7 patients. Median age at time of diagnosis of patients with IGH translocations was 62 (45-82), 29 patients were males. The median time to initial treatment (TTT) of all 39 patients with IGH translocations was 3.1 years. The median TTT for patients with IGH/BCL-2 was 3.6 years; 70% of patients required treatment by 5 years. The median TTT for IGH/BCL-3 patients was significantly shorter, 1.5 years, p=0.017, with all patients requiring therapy 3 years from diagnosis (see Figure 1).

Conclusion: The presence of IGH translocations in CLL appears to be associated with rapid disease progression and the need for an early initiation of therapy. The IGH partner gene seems to be important; IGH/BCL-3 fusion is associated with a worse prognosis than IGH/BCL-2. Further studies on the biological significance of IGH translocations in CLL are warranted and continue at our institution.

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Topics:
chronic b-cell leukemias, chronic lymphocytic leukemia, genes, immunoglobulin measurement, translocation (genetics), disease progression, fluorescent probes, cancer, cyclin d1, dna probes

Author notes

Disclosure:Consultancy: Celgene (NE Kay). Research Funding: Bayer (TD Shanafelt and NE Kay) and Hospira (NE Kay).

2007, The American Society of Hematology
2007
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