Molecular heterogeneity of the NUP98/HOXA9 fusion transcript in myelodysplastic syndromes associated with t(7;11)(p15;p15).

The reciprocal translocation t(7;11)(p15;p15) has been reported as occurring mainly in acute myelogenous leukaemia (AML) and the acute phase of chronic myelogenous leukaemia (CML). This translocation in AML involves both the nucleoporin gene NUP98 on 11p15 and the homeobox gene HOXA9 on 7p15. The invariant chimaeric NUP98/HOXA9 transcripts are a result of the fact that each breakpoint of the NUP98 and the corresponding breakpoint of the HOXA9 gene cluster occur within the same intron. Only one patient with myelodysplastic syndromes (MDS) carrying this chromosome aberration has been reported, but this study did not involve molecular analysis. We describe two patients with MDS associated with t(7;11): patient 1 was a Japanese man diagnosed with chronic myelomonocytic leukaemia; patient 2 was a Japanese woman with refractory anaemia with excess of blasts in transformation. Within a year both patients developed AML and showed multidrug resistance to chemotherapy. Southern blot analysis showed rearrangements of the NUP98 gene of the two patients and the HOXA9 gene of patient 2. Patient 1 had two types of the novel NUP98/HOXA9 fusion transcripts. Each of them lacked the common 141 bp NUP98 exon which was contained in the NUP98/HOXA9 fusion transcripts detected in patient 2 and the reported AML cases. These data indicated that t(7;11) could determine the development of various myeloid leukaemias and that the resultant chimaeric transcripts are heterogenous.