A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently rearranged at disease progression of chronic myeloid leukemia and forms a fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23).

The pathogenetic role of the P210 BCR/ABL1 fusion gene in the chronic phase of chronic myeloid leukemia (CML) has been well established.In contrast, the genetic mechanisms underlying the disease progression into the accelerated phase (AP) and the final blast crisis (BC) remain poorly understood. We have previously identified (A. Barbouti et al., Genes Chromosomes Cancer, 35: 127-137, 2002) two cryptic balanced translocations, t(7;17)(p15;q23) and t(7;17)(q32-34;q23), in CML AP/BC using multicolor fluorescence in situ hybridization. In this study, we show that a novel gene in 17q23, Musashi-2 (MSI2), encoding a putative RNA-binding protein, is rearranged in both cases and that a MSI2/HOXA9 fusion gene is formed in the case with the 7p15 breakpoint. The identified in-frame MSI2/HOXA9 fusion transcript retains both of the RNA recognition motif domains of MSI2, which is fused to the homeobox domain of HOXA9, and is likely to play an important role in the disease progression of CML.