B lymphoblastic leukemia

Only one case to date: a 3-year-old female child (Yuki et al., 2004; Prima et al., 2005; Liu et al., 2016).

The genes were fused in-frame between exon 6 of MEF2D and exon 7 of DAZAP1 (MEF2D/DAZAP1), as well as, between exon 6 of DAZAP1 and exon 7 of MEF2D (DAZAP1/MEF2D). Sequencing of the RT-PCR products confirmed in-frame fusions between MEF2D (codon 222) and DAZAP1 (codon 155) in both chimeric transcripts (Yuki et al., 2004).

Both chimeric transcripts, MEF2D/DAZAP1 and DAZAP1/MEF2D, whose sequences indicated in-frame fusions between MEF2D and DAZAP1 were expressed in bone marrow cells (Yuki et al., 2004).

MEF2D/DAZAP1 and DAZAP1/MEF2D proteins were both located in the nucleus, MEF2D/DAZAP1 was able to form dimers with MEF2D and HDAC4. Furthermore, exogenous expression of MEF2D/DAZAP1 and DAZAP1/MEF2D promoted the growth of HeLa cells (Yuki et al., 2004).

MEF2D/DAZAP1 and/or DAZAP1/MEF2D contribute to leukemogenesis by altering signaling pathways normally regulated by wild-type MEF2D and DAZAP1. MEF2D/DAZAP1 binds avidly and specifically to DNA and is a substantially more potent transcriptional activator, than MEF2D and also may associate more strongly with other proteins involved in transcriptional regulation (e.g. HDAC4). MEF2D/DAZAP1 might immediately activate transcription of genes crucial for lymphocyte growth and/or survival such as IL2 (interleukin-2), a known transcriptional target of MEF2D in T-cells. As well, MEF2D/DAZAP1 could contribute to leukemogenesis via dysregulated activation of MAPK-mediated cell proliferation pathways. These alterations may confer more potent transforming properties to MEF2D/DAZAP1, which can be further augmented by coexpression with the reciprocal DAZAP1/MEF2D chimera, which retains sequence-specific RNA binding properties (Prima et al., 2005).

MEF2D/DAZAP1