A proportion of cytogenetic abnormalities in myelodysplastic syndromes (MDS) and 
acute myeloid leukaemia (AML) may escape detection by high-resolution genomic 
technologies, but can be identified by conventional cytogenetic and molecular 
analysis. Here, we report the detection of a reciprocal translocation 
t(7;21)(p22;q22) in the marrow of two adults with MDS and AML, using 
conventional cytogenetic analysis and fluorescence-in situ-hybridization (FISH). 
Reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis 
identified a fusion between RUNX1 and the gene encoding ubiquitin specific 
peptidase-42 (USP42), with splice-variants and variable break-points within 
RUNX1. Combined cytomorphology and FISH studies in MDS marrow revealed abnormal 
RUNX1 signals within megakaryocytes, suggesting that the acquisition of 
t(7;21)(p22;q22) does not confer complete differentiation arrest and may 
represent an early genetic event in leukaemogenesis. Single nucleotide 
polymorphism-arrays failed to detect additional sub-microscopic genomic changes 
predisposing to or associated with t(7;21). Molecular analysis of 100 MDS and 
AML marrow specimens by RT-PCR did not reveal new cases with the RUNX1-USP42 
fusion. Thus, our studies have identified t(7;21)(p22;q22) as a rare but 
recurrent abnormality in MDS/AML, with the existence of alternative spliced 
forms of the RUNX1-USP42 transcript in different patients. Further studies are 
required to identify the potential contribution of these splice-variants to 
disease heterogeneity.