Concurrent Activation of c-MYC and Bcl-6 by Translocation of Both Oncogenes to the Same Immunoglobulin Heavy Chain Locus

Abstract Concurrent occurrence of 2 specific chromosome translocations is a relatively rare phenomenon and only occasionally has been described in hematologic malignancies. Individual cases concurrently harboring c-MYC/immunoglobulin (Ig)H and Bcl-6/IgH rearrangements have been previously reported in B-cell malignancies; however, the occurrence of 3-way translocations simultaneously affecting 3 key genes involved in the pathogenesis was described only in individual cases. This report describes a patient diagnosed with acute lymphoblastic leukemia with genetic alterations concurrently affecting the c-MYC, Bcl-6, and IgH loci in addition to the rearrangement of the long arm of chromosome 1. Our case might be of interest because of the: (1) concurrent translocations of Bcl-6 and c-MYC oncogenes to the same IgH loci as a result of a 3-way recombination; (2) disruption of the bcl-6 gene because of the cryptic insertion of IgH in 3q27; (3) presence of jumping translocation affecting the long arm of chromosome 1; and (4) further illustration of the utility of fluorescence in situ hybridization studies in the identification of cryptic and complex translocations in routine diagnosis. Concurrent translocations of 2 key oncogenes to the same immunoglobulin loci demonstrate novel features of instability of bcl-6 and IgH genes and might present a novel mechanism of gene activation in B-cell malignancies.