cDNA cloning, expression pattern, and chromosomal localization of Mlf1, murine homologue of a gene involved in myelodysplasia and acute myeloid leukemia

The NPM-MLF1 fusion protein is expressed in blasts from patients with myelo dysplasia/acute myeloid leukemia (MDS/AML) containing the t(3;5) chromosoma l rearrangement. Nucleophosmin (NPM), a previously characterized nucleolar phosphoprotein, contributes to two other fusion proteins found in lympho-he matopoietic malignancies, anaplastic large cell lymphoma (NPM-ALK) and acut e promyelocytic leukemia (NPM-RAR alpha), By contrast, the function off the carboxy-terminal fusion partner, myelodysplasia/myeloid leukemia factor 1 (MLF1), is unknown. To aid in understanding normal MLF1 function, we isolat ed the murine cDNA, determined the chromosomal localization of Mlf1, and de fined its tissue expression by in situ hybridization, Mlf1 was highly simil ar to its human homologue (86% and 84% identical nucleotide and amino acid sequence, respectively) and mapped to the central region of chromosome 3, w ithin a segment lacking known mouse mutations. Mlf1 tissue distribution was restricted during both development and postnatal life, with high levels pr esent only in skeletal, cardiac, and selected smooth muscle, gonadal tissue s, and rare epithelial tissues including the nasal mucosa and the ependyma/ choroid plexus in the brain. Mlf1 transcripts were undetectable in the lymp ho-hematopoietic organs of both the embryonic and adult mouse, suggesting t hat NPM-MLF1 contributes to the genesis of MDS/AML in part by enforcing the ectopic overexpression of MLF1 within hematopoietic tissues.