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.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bone Morphogenetic Protein 2 / pharmacology
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Bone Morphogenetic Protein 2 / physiology
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Bone Morphogenetic Protein 4 / pharmacology
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Bone Morphogenetic Protein 4 / physiology
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Bone Morphogenetic Protein 6 / pharmacology
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Bone Morphogenetic Protein 6 / physiology
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Bone Morphogenetic Proteins / metabolism
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Bone Morphogenetic Proteins / pharmacology
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Bone Morphogenetic Proteins / physiology*
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Cell Differentiation / drug effects*
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Cell Differentiation / genetics
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Gene Expression Regulation, Leukemic / drug effects
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Gene Expression Regulation, Leukemic / genetics
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Granulocyte Precursor Cells / drug effects*
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Granulocyte Precursor Cells / metabolism
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Granulocyte Precursor Cells / physiology
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HL-60 Cells
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Humans
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Leukemia, Promyelocytic, Acute / genetics
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Leukemia, Promyelocytic, Acute / pathology
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Leukemia, Promyelocytic, Acute / physiopathology*
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Neoplastic Stem Cells / drug effects*
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Neoplastic Stem Cells / physiology
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism
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Tretinoin / pharmacology
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Tumor Cells, Cultured
Substances
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BMP2 protein, human
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BMP4 protein, human
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BMP6 protein, human
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Protein 6
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Bone Morphogenetic Proteins
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Oncogene Proteins, Fusion
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promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
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Tretinoin