Journal
LEUKEMIA RESEARCH
Volume 37, Issue 6, Pages 705-712Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2013.03.002
Keywords
Acute promyelocytic leukemia; Bone morphogenetic proteins; All-trans retinoic acid; Differentiation; ID genes; Cell lines; Patients
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Funding
- Croatian Ministry of Science, Education and Sports [108-1080229-0142, 108-1080229-0140, 108-1080955-3094]
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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/EBP epsilon 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/RAR alpha and negative of RAR alpha 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. (C) 2013 Elsevier Ltd. All rights reserved.
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