This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hitzler, J. K. Articles by Morris, S. W. Search for Related Content PubMed PubMed Citation Articles by Hitzler, J. K. Articles by Morris, S. W.

(American Journal of Pathology. 1999;155:53-59.)
© 1999 American Society for Investigative Pathology

Short Communication

cDNA Cloning, Expression Pattern, and Chromosomal Localization of Mlf1, Murine Homologue of a Gene Involved in Myelodysplasia and Acute Myeloid Leukemia

Johann K. Hitzler^*, David P. Witte^¶, Nancy A. Jenkins^||, Neal G. Copeland^||, Debra J. Gilbert^||, Clayton W. Naeve, A. Thomas Look^*§ and Stephan W. Morris^*§

From the Departments of Experimental Oncology^*
and Hematology-Oncology,
and the Center for Biotechnology,
St. Jude Children's Research Hospital, Memphis, Tennessee; the Department of Pediatrics,^§
University of Tennessee College of Medicine, Memphis, Tennessee; the Division of Pathology,^¶
Department of Pediatrics, University of Cincinnati Medical Center, Cincinnati, Ohio; and the Mammalian Genetics Laboratory,^||
ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland

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-RAR). 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.

This article has been cited by other articles:

				B. Falini, I. Nicoletti, N. Bolli, M. P. Martelli, A. Liso, P. Gorello, F. Mandelli, C. Mecucci, and M. F. Martelli Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias Haematologica, April 1, 2007; 92(4): 519 - 532. [Abstract] [Full Text] [PDF]

				L. N. Winteringham, R. Endersby, S. Kobelke, R. K. McCulloch, J. H. Williams, J. Stillitano, S. M. Cornwall, E. Ingley, and S. P. Klinken Myeloid Leukemia Factor 1 Associates with a Novel Heterogeneous Nuclear Ribonucleoprotein U-like Molecule J. Biol. Chem., December 15, 2006; 281(50): 38791 - 38800. [Abstract] [Full Text] [PDF]

				P. G. Giresi, E. J. Stevenson, J. Theilhaber, A. Koncarevic, J. Parkington, R. A. Fielding, and S. C. Kandarian Identification of a molecular signature of sarcopenia Physiol Genomics, April 14, 2005; 21(2): 253 - 263. [Abstract] [Full Text] [PDF]

				J.-P. Lalonde, R. Lim, E. Ingley, P. A. Tilbrook, M. J. Thompson, R. McCulloch, J. G Beaumont, C. Wicking, H. J. Eyre, G. R. Sutherland, et al. HLS5, a Novel RBCC (Ring Finger, B Box, Coiled-coil) Family Member Isolated from a Hemopoietic Lineage Switch, Is a Candidate Tumor Suppressor J. Biol. Chem., February 27, 2004; 279(9): 8181 - 8189. [Abstract] [Full Text] [PDF]

				R. Lim, L. N. Winteringham, J. H. Williams, R. K. McCulloch, E. Ingley, J. Y-H. Tiao, J.-P. Lalonde, S. Tsai, P. A. Tilbrook, Y. Sun, et al. MADM, a Novel Adaptor Protein That Mediates Phosphorylation of the 14-3-3 Binding Site of Myeloid Leukemia Factor 1 J. Biol. Chem., October 18, 2002; 277(43): 40997 - 41008. [Abstract] [Full Text] [PDF]

				J. L. Kutok and J. C. Aster Molecular Biology of Anaplastic Lymphoma Kinase-Positive Anaplastic Large-Cell Lymphoma J. Clin. Oncol., September 1, 2002; 20(17): 3691 - 3702. [Abstract] [Full Text] [PDF]