Retinoic acid signaling in myelopoiesis.
OBJECTIVE
For decades, retinoic acid has been known to alter the proliferation and differentiation of myeloid cells. Currently, retinoic acid is a front-line agent in the treatment of certain forms of acute myelogenous leukemia. In this review, we focus on recent advances in our understanding of the mechanisms by which retinoids affect growth and proliferation of myeloid cells and contribute to the pathogenesis of leukemia. We have not attempted to summarize the related clinical literature.


RESULTS
The past 2 years have yielded important understanding of the mechanisms by which retinoids and their nuclear receptors interact with other signal transduction pathways and transcription factors to modify chromatin, alter gene expression, and participate in normal myeloid differentiation and leukemogenesis. Important advances regarding cell biology, molecular biology, biochemistry, and animal studies of retinoids and myeloid differentiation are reviewed.


CONCLUSIONS
Greater understanding of the role of retinoids and their receptors in myeloid cell growth and differentiation provides important insight into normal myelopoiesis. These findings have resulted in successful rational approaches to the treatment of acute leukemia and provide the promise of improved treatments in the near future.
Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Karen
K
Drumea
Zhong-fa
ZF
Yang
Alan
A
Rosmarin
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D038042:Myelopoiesis / Q000187:drug effects / Q000502:physiology*; D009196:Myeloproliferative Disorders / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000502:physiology; D012176:Retinoids / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
D002843:Chromatin; D015514:Oncogene Proteins, Fusion; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014157:Transcription Factors; D014212:Tretinoin