Hematopoiesis and Retinoids: Development and Disease

  title={Hematopoiesis and Retinoids: Development and Disease},
  author={Tal Oren and Justin Sher and Todd Evans},
  journal={Leukemia \& Lymphoma},
  pages={1881 - 1891}
Retinoids function as activating ligands for a class of nuclear receptors that control gene expression programs for a wide range of tissues and organs during embryogenesis and throughout life. Over the years, three sets of observations have spurred interest in the function of retinoids with respect to development and disease of hematopoietic cells. Since the 1920s, epidemiological studies indicated altered hematopoiesis in vitamin A-deficient (VAD) human populations. More recently, the ability… 

Regulation of hematopoiesis by retinoid signaling.

  • T. Evans
  • Biology, Medicine
    Experimental hematology
  • 2005

An emerging role for retinoid X receptor α in malignant hematopoiesis.

Endogenous and combination retinoids are active in myelomonocytic leukemias

Insight is provided into the basal presence of natural retinoids in leukemias in vivo and a potential strategy for clinical retinoid combination regimens in leukedmias beyond APL is provided.

Retinoic Acid Receptors in Acute Myeloid Leukemia Therapy

The RA signaling pathway in normal and malignant hematopoiesis is reviewed, and the advantages and the limitations related to retinoid therapy in acute myeloid leukemia are discussed.

ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia

It is demonstrated that ZRF1 depletion decreases cell proliferation, induces apoptosis and enhances cell differentiation in human AML cells, and suggested that Z RF1 inhibition could be a novel strategy to be explored for AML treatment.

Rara haploinsufficiency modestly influences the phenotype of acute promyelocytic leukemia in mice.

Data show that Rara haploinsufficiency can cooperate with PML-RARA to influence the pathogenesis of APL in mice, but that PML -RARA is the t(15;17) disease-initiating mutation.

ZRF1: a novel epigenetic regulator of stem cell identity and cancer

Increasing evidence points to ZRF1 as a novel target for therapy of neurodegenerative diseases and cancer.

Identification of Converging Pathways in the pathogenesis of NPM-RARA Variant Acute Promyelocytic Leukemia

The goals of this thesis were to determine genes and pathways deregulated in variant APL that can serve as cooperating events in APL, through candidate pathways analysis and high-throughput gene expression profiling, and to suggest a greater ability on the part of NPM-RARA cells to survive in the presence of TNFα.



Retinoid signaling regulates primitive (yolk sac) hematopoiesis.

It is proposed that vitamin A-derived retinoids are required for normal yolk sac hematopoiesis and that an embryonic retinoid-BMP-GATA-2 signaling pathway controls progenitor cell survival relevant to primitive hematopoliesis.

Modeling acute promyelocytic leukemia in the mouse: new insights in the pathogenesis of human leukemias.

While the X-RARalpha fusion gene is crucial for leukemogenesis, the presence of RARalpha-X and the inactivation of X function are critical in modulating the onset as well as the phenotype of the leukemia.

Vitamin A deficiency in mice causes a systemic expansion of myeloid cells.

It is shown that retinoids critically control the homeostasis of myeloid cell population in vivo and suggests that deficiency in this signaling pathway may contribute to various myeloproliferative disorders.

Role of Promyelocytic Leukemia (Pml) Protein in Tumor Suppression

It is demonstrated that PML acts in vivo as a tumor suppressor by rendering the cells resistant to proapoptotic and differentiating stimuli, and PML haploinsufficiency and the functional impairment of PML by PMLRARα are critical events in APL pathogenesis.

Retinoid acid supports granulocytic but not erythroid differentiation of myeloid progenitors in normal bone marrow cells.

A specific effect of retinoid on late myeloid precursors is suggested and places retinoids as possible candidates for enhancement of normal granulocytic differentiation.

Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis.

It is proposed that the function of CRBP is to store and release retinol where high levels of RA are required for specific morphogenetic processes, while CRABP serves to sequester RA in regions where normal developmental functions require RA levels to be low.

Embryonic retinoic acid synthesis is essential for early mouse post-implantation development

It is established that RA synthesized by the post-implantation mammalian embryo is an essential developmental hormone whose lack leads to early embryo death.

A developmental transition in definitive erythropoiesis: erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4.

It is proposed that Epo expression is regulated during the E9.5--E 11.5 phase of fetal liver erythropoiesis by RXR alpha and retinoic acid, and that expression then becomes dominated by HNF4 activity from E11.5 onward, which may be responsible for switching regulation of Epoexpression from retinoi acid control to hypoxic control, as is found throughout the remainder of life.

Effects of retinoid deficiency on the development of the heart and vascular system of the quail embryo

In vivo studies show that the basis for the retinoid-deficient defect is the failure of the primitive heart tubes to open at their posterior end, thus preventing the formation of omphalomesenteric veins normally connecting the embryonal with the extraembryonal circulatory system.