TY - JOUR
T1 - cDNA cloning, expression pattern, and chromosomal localization of Mlf1, murine homologue of a gene involved in myelodysplasia and acute myeloid leukemia
AU - Hitzler, Johann K.
AU - Witte, David P.
AU - Jenkins, Nancy A.
AU - Copeland, Neal G.
AU - Gilbert, Debra J.
AU - Naeve, Clayton W.
AU - Look, A. Thomas
AU - Morris, Stephan W.
N1 - Funding Information:
Supported by the Pediatric Scientist Development Program through a grant from St. Jude Children's Research Hospital (supporting J. K. H.), the American Heart Association, Ohio-West Virginia affiliate (SW-96–43) (to D. P. W.), the Department of Health and Human Services under contract with ABL (to N. A. J., N. G. C., and D.J.G.), National Cancer Institute grants CA 76301 (to S. W. M.) and Cancer Center Support (CORE) grant CA 27165 , and by the American Lebanese Syrian Associated Charities, St. Jude Children's Research Hospital.
PY - 1999/7
Y1 - 1999/7
N2 - The NPM-MLF1 fusion protein is expressed in blasts from patients with myelodysplasia/acute myeloid leukemia (MDS/AML) containing the t(3;5) chromosomal rearrangement. Nucleophosmin (NPM), a previously characterized nucleolar phosphoprotein, contributes to two other fusion proteins found in lympho-hematopoietic malignancies, anaplastic large cell lymphoma (NPM-ALK) and acute promyelocytic leukemia (NPM-RARα). By contrast, the function of the carboxy-terminal fusion partner, myelodysplasia/myeloid leukemia factor 1 (MLF1), is unknown. To aid in understanding normal MLF1 function, we isolated the murine cDNA, determined the chromosomal localization of Mlf1, and defined its tissue expression by in situ hybridization. Mlf1 was highly similar to its human homologue (86% and 84% identical nucleotide and amino acid sequence, respectively) and mapped to the central region of chromosome 3, within a segment lacking known mouse mutations. Mlf1 tissue distribution was restricted during both development and postnatal life, with high levels present only in skeletal, cardiac, and selected smooth muscle, gonadal tissues, and rare epithelial tissues including the nasal mucosa and the ependyma/choroid plexus in the brain. Mlf1 transcripts were undetectable in the lympho-hematopoietic organs of both the embryonic and adult mouse, suggesting that NPM-MLF1 contributes to the genesis of MDS/AML in part by enforcing the ectopic overexpression of MLF1 within hematopoietic tissues.
AB - The NPM-MLF1 fusion protein is expressed in blasts from patients with myelodysplasia/acute myeloid leukemia (MDS/AML) containing the t(3;5) chromosomal rearrangement. Nucleophosmin (NPM), a previously characterized nucleolar phosphoprotein, contributes to two other fusion proteins found in lympho-hematopoietic malignancies, anaplastic large cell lymphoma (NPM-ALK) and acute promyelocytic leukemia (NPM-RARα). By contrast, the function of the carboxy-terminal fusion partner, myelodysplasia/myeloid leukemia factor 1 (MLF1), is unknown. To aid in understanding normal MLF1 function, we isolated the murine cDNA, determined the chromosomal localization of Mlf1, and defined its tissue expression by in situ hybridization. Mlf1 was highly similar to its human homologue (86% and 84% identical nucleotide and amino acid sequence, respectively) and mapped to the central region of chromosome 3, within a segment lacking known mouse mutations. Mlf1 tissue distribution was restricted during both development and postnatal life, with high levels present only in skeletal, cardiac, and selected smooth muscle, gonadal tissues, and rare epithelial tissues including the nasal mucosa and the ependyma/choroid plexus in the brain. Mlf1 transcripts were undetectable in the lympho-hematopoietic organs of both the embryonic and adult mouse, suggesting that NPM-MLF1 contributes to the genesis of MDS/AML in part by enforcing the ectopic overexpression of MLF1 within hematopoietic tissues.
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U2 - 10.1016/S0002-9440(10)65098-5
DO - 10.1016/S0002-9440(10)65098-5
M3 - Article
C2 - 10393836
AN - SCOPUS:0033060171
SN - 0002-9440
VL - 155
SP - 53
EP - 59
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -