title: Deregulated expression of c-myc in megakaryocytes of transgenic mice increases megakaryopoiesis and decreases polyploidization.
abstract: Platelets, essential for vascular integrity and hemostasis, fragment from polyploid megakaryocytes, characterized by their endomitotic cell cycle. We studied the influence of overexpression of c-myc oncogene on megakaryopoiesis and endomitosis in vivo, using transgenic mice carrying c-myc fused to the estrogen receptor under the control of the platelet factor 4 (PF4) megakaryocyte-specific promoter. The rationale behind this strategy was to obtain controlled overexpression of an active c-Myc, depending on the estrogen level in the mouse circulation. Analysis of these transgenic mice revealed that the bone marrow of female transgenic mice or of estrogen-injected male transgenic mice, but not of age-matched transgenic males nor nontransgenic females, contained frequent immature myeloid cells and an increased number of megakaryocytes. Deregulated expression of c-Myc shifted the normal ploidy profile of megakaryocytes due to a significant increase in proliferating megakaryocytes and a decrease in the fraction of ploidizing cells. These transgenic mice represent a novel in vivo model for a Myc-induced myeloproliferative disorder which can be controlled.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02139, USA.
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Kamen
authors.forename: C W
authors.initials: CW
authors.lastname: Jackson
authors.forename: R D
authors.initials: RD
authors.lastname: Cardiff
authors.forename: K
authors.initials: K
authors.lastname: Ravid
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D004920:Erythropoiesis / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008533:Megakaryocytes / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis; D009196:Myeloproliferative Disorders / Q000235:genetics; D010978:Platelet Factor 4 / Q000235:genetics; D011123:Polyploidy; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins; D013154:Spleen / Q000473:pathology; D013249:Sternum / Q000473:pathology
chemical_list: D004967:Estrogens; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D010978:Platelet Factor 4