Deadly fusion

Acute megakaryoblastic leukemia (AMKL) kills its young victims within a matter of months; and AMKL is associated with a chromosomal translocation t(1;22)(p13;q13). In the July issue of Nature Genetics, Ma et al. report the identification of two novel genes that are fused at the translocation breakpoint (Nature Genetics 2001, 28:220-221). They used a cloning strategy based on fluorescence in situ hybridization (FISH) to define the breakpoint and to recover bacterial artificial chromosome (BAC) clones covering the region. From these, they cloned a chromosome 22 gene, named MKL1 (megakaryoblastic leukemia-1) that contains a SAP DNA-binding motif and may be involved in chromatin remodelling. MKL1 is fused to a gene on chromosome 1 called RBM15 (RNA-binding motif protein 15); it encodes RNA-recognition motifs and resembles the Drosophila gene spen. The authors speculate that the RMM15-MKL1 fusion protein causes aberrant RNA processing and signalling that disrupts megakaryoblast differentiation and/or proliferation.