NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia

The role of the BCR-ABL fusion gene in the pathogenesis of the chronic phas e of chronic myelogenous leukemia (CML) has been well established. Several additional genetic changes have been reported to occur, at varying frequenc ies, during disease progression to "accelerated" and "blast crisis" phases. The NUP98 gene localized to chromosome band 11p15 has been found at the br eakpoints of several distinct chromosomal translocations in patients with b oth de novo and therapy-related myelodysplastic syndromes (MDS) and acute m yelogenous leukemia (AML). Using combined cytogenetic and molecular analyse s, we have found rearrangements of the NUP98 gene in the leukemic cells of two patients with Philadelphia chromosome-positive CML, during disease evol ution. As expected, analysis of the t(7;11)(p15;p15) from one of the patien ts showed an in-frame NUP98-HOXA9 fusion. The fusion points were similar to previously reported NUP98-HOXA9 fusion points from patients with MDS/AML. Our results indicate that the NUP98 gene is an additional, albeit infrequen t, genetic target during clonal evolution of CML. (C) 2001 Wiley-Liss. Inc.