A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors

• Published in: Cell Vol. 63; no. 6; pp. 1137 - 1147
• Main Authors: Souyri, Michèle, Vigon, Isabelle, Penciolelli, Jean-François, Heard, Jean-Michel, Tambourin, Pierre, Wendling, Françoise
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 21.12.1990; Cell Press
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Bone Marrow Cells; capsid protein; Cell Line; Cell Transformation, Neoplastic; Colony-Forming Units Assay; cytokines; DNA, Viral - genetics; DNA, Viral - isolation & purification; Friend leukemia virus; Fundamental and applied biological sciences. Psychology; Gene Library; Genes, Viral; Genetics; Hematopoietic Stem Cells - cytology; immortalization; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Nude; Microbiology; Molecular Sequence Data; Muridae; Oncogenes; progenitors; proviruses; receptors; Receptors, Cell Surface - genetics; Retroviridae - genetics; RNA, Viral - genetics; RNA, Viral - isolation & purification; transduction; Viral Envelope Proteins - genetics; Virology; Oncovirinae; Retroviridae; Hematopoietic cell; V-Onc gene; Cell transformation; Virus; Cell line; Gene; Type C oncovirus; Bone marrow; Murine leukemia virus; Molecular cloning; Virus envelope; Aminoacid sequence; Biological receptor
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(90)90410-G

The myeloproliferative leukemia virus (MPLV) is an acute leukemogenic murine replication-defective retrovirus. By sequencing the envelope gene of a biologically active MPLV clone, we found that this region comprises a novel oncogene named v- mpl in phase with two parts of the Friend murine leukemia virus envelope gene. The MPLV env region could encode an env-mpl fusion polypeptide that presents the characteristics of a transmembrane protein. We show that in vitro infection of bone marrow cells with helper-free MPLV readily yields immortalized factor-independent hematopoietic cell lines of different lineages. In mice, the c- mpl proto-oncogene is expressed in hematopoietic tissues as a 3 kb mRNA. Since v- mpl shares strong structural analogies with the hematopoietin receptor superfamily, it is likely that MPLV has transduced a truncated form of an as yet unidentified hematopoietic growth factor receptor.