title: Bone morphogenetic proteins regulate differentiation of human promyelocytic leukemia cells.
abstract: We investigated the role of bone morphogenetic proteins (BMPs) in suppression of all-trans retinoic acid (ATRA)-mediated differentiation of leukemic promyelocytes. In NB4 and HL60 cell lines, BMPs reduced the percentage of differentiated cells, and suppressed PU.1 and C/EBPε gene expression induced by ATRA. BMP and ATRA synergized in the induction of ID genes, causing suppression of differentiation. In primary acute promyelocytic leukemia bone-marrow samples, positive correlation of PML/RARα and negative of RARα with the expression of BMP-4, BMP-6 and ID genes were found. We concluded that BMPs may have oncogenic properties and mediate ATRA resistance by a mechanism that involves ID genes.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Center Zagreb, Zagreb, Croatia. itopic@mef.hr
authors.forename: Iva
authors.initials: I
authors.lastname: Topić
authors.forename: Marina
authors.initials: M
authors.lastname: Ikić
authors.forename: Sanja
authors.initials: S
authors.lastname: Ivčević
authors.forename: Nataša
authors.initials: N
authors.lastname: Kovačić
authors.forename: Ana
authors.initials: A
authors.lastname: Marušić
authors.forename: Rajko
authors.initials: R
authors.lastname: Kušec
authors.forename: Danka
authors.initials: D
authors.lastname: Grčević
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology / Q000502:physiology; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D042381:Granulocyte Precursor Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525816:BMP6 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin