Although there are conflicting data regarding prognostic implications of isolated MYC aberrancy in these non-BLs, the co-occurrence of MYC rearrangements and either the antiapoptotic gene B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) or the transcriptional repressor BCL6 leads to an entity termed double-hit B-cell lymphoma (DHL) (or triple-hit if all 3 abnormalities are observed) with a particularly poor prognosis and no established treatment paradigms.
Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug.
We examined the distribution of IgVH and BCL-6 gene mutations in 95 well-characterized patients with Binet stage A B-CLL, and correlated them with clinical, laboratory, cytogenetic findings and disease progression.
These results indicate that a subset of B-CLL derives from a cell that has been exposed to the somatic hypermutation mechanism and support the hypothesis that BCL-6 mutations result from the same process that targets immunoglobulin genes.
Overall, the distribution of BCL-6 and IgV mutations in B-CLL reinforce the notion that this leukemia is histogenetically heterogeneous and that a substantial subgroup of these lymphoproliferations derives from post-germinal center B cells.