ASH2L: alternative splicing and downregulation during induced megakaryocytic differentiation of multipotential leukemia cell lines

Drosophila ash2 is a member of the trxG gene super family, some human homol ogues of which are involved in hematopoiesis and leukemia. We report here t he identification of the human homologue of Drosophila ash2 and its alterna tive splicing isoform. ASH2L1 and ASH2L2. ASH2L proteins are 60% homologous to Drosophila ash2. ASH2L also has a zinc finger motif (C2C2) although it is not identical to that in ASH2. Expression profile analysis showed that t he amount of ASH2L transcripts is extremely high in fetal liver, testis, an d leukemia cell lines with erythroid and megakaryocytic potential such as K 562, Hel, and Dami. We treated these cells with differentiation inducers ph orbol ester and hemin. We found that ASH2L is downregulated rapidly and dra matically in K562, Hel, and Dami cells during phorbol ester induced differe ntiation with megakaryocytic features. However, its expression is maintaine d at a high level during erythroid differentiation of K562 cells induced wi th hemin. These results suggest that ASH2L plays a role in hematopoiesis an d is associated with some special kinds of leukemia.