Non-muscle myosin heavy chain (MYH9): A new partner fused to ALK in anaplastic large cell lymphoma

In aniplastic large cell lymphoma, the ALK gene at 2p23 is known to be fused to NPM, TPM3, TPM4, TFG, ATIC, CLTC, MSN, and ALO17. All of these translocations result in the expression of chimeric ALK transcripts that are translated into fusion proteins with tyrosine kinase activity and oncogenic properties. We report a case showing a restricted cytoplasmic staining pattern of ALK and a novel chromosomal abnormality, t(2;22)(p23;q11.2), demonstrated by fluorescence in situ hybridization analysis. The result of 5' PACE analysis showed that the ALK gene was fused in-frame to a portion of the non-muscle myosin heavy, chain gene, MYH9; Nucleotide sequence of the Willi chimeric cl revealed that the ALK breakpoint was different from all those previously reported. It is localized in the same exonic sequence as MMSN-ALK but 6 bp downstream, resulting in an in-frame fusion of the two partner proteins. In contrast to t he previously reported ALK fusion proteins, MYH9-ALK may lack a functional oligomerization domain. However, biochemical analysis showed that the new fusion protein is tyrosine phosphorylated in vivo but seems to lack tyrosine kinase activity in vitro. If further investigations confirm this latter result, the in vivo tyrosine phosphorylation of MYH9-ALK protein could involve mechanisms different from those described in the other ALK hybrid proteins. (C) 2003 Wiley-Liss, Inc.