Involvement of Dock8 in a Paracentric Inversion Affecting the Derivative Chromosome 9 in a Case of Philadelphia Positive Chronic Myeloid Leukemia

Chronic Myeloid Leukemia (CML) is a myeloproliferative disease in which the presence of the BCR-ABL1 fusion gene is the major criterion for diagnosis, consistently associated with specific clinical, laboratory and morphological features. Some cases present with a variant t(9;22) translocation, involving one or more chromosomes. Here we describe a 66 year-old woman with CML showing a variant t(9;22)(q34.12;q11.23) translocation. Classical cytogenetic analysis displayed the presence of additional chromosomal material of unknown origin at the telomere of the short arm of the derivative chromosome 9 [der(9)]. FISH experiments revealed that this material derived from chromosome 22. Using appropriate bacterial artificial chromosome probes, we disclosed that DOCK8 (9p24.3) was interrupted by a paracentric inversion breakpoint on the short arm of der(9). The partner breakpoint was located within the translocated sequence of BCR that was then juxtaposed to DOCK8, without the formation of any fusion gene. As observed by real-time quantitative PCR, DOCK8 was not significantly altered in its expression levels, although we could not exclude the coding of truncated DOCK8 transcript isoforms produced because of the rearrangement. Interestingly, this gene was described as homozygously deleted in many cancer types, suggesting a possible role of this gene as a tumor suppressor. To the best of our knowledge, this is the first report describing the involvement of DOCK8 in CML, although its role in the leukemogenesis requires further clarifications