PMID- 11588055
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 98
IP  - 8
DP  - 2001 Oct 15
TI  - Lineage restriction of the RARalpha gene expression in myeloid differentiation.
PG  - 2563-7
AB  - To better understand the role of retinoids in myelopoiesis, expression of the 
      retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors 
      [RXRs]) were examined during differentiation of factor-dependent cell-Paterson 
      (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in 
      undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform). 
      Following induction of myelomonocytic differentiation with granulocyte and 
      granulocyte-macrophage colony-stimulating factors, a dramatic increase in 
      RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast, 
      expression of both RARalpha isoforms was rapidly extinguished upon induction of 
      erythroid differentiation with erythropoeitin (EPO). A modest induction of 
      RXRalpha expression was seen, particularly during differentiation in the 
      myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained 
      unchanged, irrespective of differentiation pathway. Consistent with the gene 
      expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic 
      and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, 
      these results suggest that erythropoiesis and granulopoiesis require diminished 
      and enhanced RARalpha activities, respectively, which at physiological 
      all-trans-retinoic acid (RA) concentrations may be accomplished by reciprocal 
      effects of EPO and myelomonocytic growth factors on its expression. This 
      hypothesis is corroborated by data showing that RA, which positively regulates 
      RARalpha2 expression, can exert inhibitory effects on erythroid differentiation.
FAU - Zhu, J
AU  - Zhu J
AD  - Leukaemia Research Fund Centre and Section of Gene Function and Regulation at the 
      Institute of Cancer Research, Chester Beatty Laboratories, London, United 
      Kingdom.
FAU - Heyworth, C M
AU  - Heyworth CM
FAU - Glasow, A
AU  - Glasow A
FAU - Huang, Q H
AU  - Huang QH
FAU - Petrie, K
AU  - Petrie K
FAU - Lanotte, M
AU  - Lanotte M
FAU - Benoit, G
AU  - Benoit G
FAU - Gallagher, R
AU  - Gallagher R
FAU - Waxman, S
AU  - Waxman S
FAU - Enver, T
AU  - Enver T
FAU - Zelent, A
AU  - Zelent A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA Primers)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 11096-26-7 (Erythropoietin)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 5688UTC01R (Tretinoin)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Bone Marrow/physiology
MH  - Bone Marrow Cells/cytology
MH  - Cell Differentiation/genetics/*physiology
MH  - Cells, Cultured
MH  - DNA Primers
MH  - Erythropoietin/genetics
MH  - *Gene Expression Regulation/drug effects
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - HL-60 Cells
MH  - Hematopoietic Stem Cells/cytology/drug effects/physiology
MH  - Humans
MH  - Leukemia
MH  - Models, Biological
MH  - Receptors, Retinoic Acid/drug effects/*genetics
MH  - Retinoic Acid Receptor alpha
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2001/10/06 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/06 10:00
PHST- 2001/10/06 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/06 10:00 [entrez]
AID - S0006-4971(20)56948-6 [pii]
AID - 10.1182/blood.v98.8.2563 [doi]
PST - ppublish
SO  - Blood. 2001 Oct 15;98(8):2563-7. doi: 10.1182/blood.v98.8.2563.