PMID- 30315825
OWN - NLM
STAT- MEDLINE
DCOM- 20190326
LR  - 20190326
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 69
DP  - 2019 Jan
TI  - TCF4 promotes erythroid development.
PG  - 17-21.e1
LID - S0301-472X(18)30858-0 [pii]
LID - 10.1016/j.exphem.2018.10.002 [doi]
AB  - Transcription factor 4 (TCF4) is implicated in lymphoid cell differentiation and 
      its expression predicts outcome in acute myeloid leukemia. Here, we investigated 
      the role of TCF4 in myelopoiesis. Overexpression of TCF4 (TCF4(OE)) in umbilical 
      cord blood (UCB) cells resulted in a twofold increase in erythroid colony forming 
      units (CFU-Es), whereas knock-down (KD) of TCF4 (TCF4(KD)) caused a dramatic 
      decrease in the number of erythroid colonies. In megakaryocyte CFUs (CFU-MKs), 
      both TCF4(KD) and TCF4(OE) inhibited MK colony formation. TCF4 did not have an 
      impact on granulocyte, macrophage, or granulocyte-macrophage colonies or on the 
      proportion of MK-erythrocyte progenitors (MEPs) in culture. Because TCF4 affects 
      erythroid/MK development and these lineages are affected in myelodysplastic 
      syndrome (MDS), we studied the impact of TCF4 expression in this disease. MDS 
      patients with high (>/=median) TCF4 mRNA expression had higher hemoglobin (Hb) 
      levels than MDS patients with low TCF4 expression (mean 9.0 vs. 8.55 g/dL, 
      p = 0.02). Overall, TCF4 mRNA expression was lower in hematopoietic stem cells, 
      common myeloid progenitors, and MEPs from MDS patients, but not in 
      granulocyte-macrophage progenitors, compared with healthy controls. Therefore, in 
      cell fractions with erythroid lineage potential, TCF4 is expressed less in MDS 
      patients than in healthy controls. This correlates with the low overall Hb levels 
      seen in MDS patients compared with healthy individuals and is consistent with the 
      positive impact of TCF4 on erythroid development while not having impact on white 
      colonies. These results indicate a role for TCF4 as a novel factor in 
      erythroid-megakaryocytic differentiation.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - In 't Hout, Florentien E M
AU  - In 't Hout FEM
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - van Duren, Jolanda
AU  - van Duren J
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - Monteferrario, Davide
AU  - Monteferrario D
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - Brinkhuis, Emma
AU  - Brinkhuis E
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - Mariani, Niccolo
AU  - Mariani N
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - Westers, Theresia M
AU  - Westers TM
AD  - Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer 
      Center Amsterdam, Amsterdam, The Netherlands.
FAU - Chitu, Dana
AU  - Chitu D
AD  - HOVON Data Center, Erasmus University Medical Center-Daniel den Hoed, Rotterdam, 
      The Netherlands.
FAU - Nikoloski, Gorica
AU  - Nikoloski G
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - van de Loosdrecht, Arjan A
AU  - van de Loosdrecht AA
AD  - Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer 
      Center Amsterdam, Amsterdam, The Netherlands.
FAU - van der Reijden, Bert A
AU  - van der Reijden BA
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands.
FAU - Jansen, Joop H
AU  - Jansen JH
AD  - Department of Laboratory Medicine, Laboratory of Hematology, Radboud University 
      Medical Centre, Nijmegen, The Netherlands. Electronic address: 
      Joop.Jansen@Radboudumc.nl.
FAU - Huls, Gerwin
AU  - Huls G
AD  - Department of Hematology, University Medical Centre Groningen, Groningen, The 
      Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20181010
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Hemoglobins)
RN  - 0 (TCF4 protein, human)
RN  - 0 (Transcription Factor 4)
SB  - IM
MH  - *Cell Differentiation
MH  - Cells, Cultured
MH  - Erythroid Precursor Cells/*metabolism/pathology
MH  - Fetal Blood/metabolism
MH  - Gene Expression Regulation
MH  - *Hemoglobins/biosynthesis/genetics
MH  - Humans
MH  - Megakaryocytes/pathology
MH  - Myelodysplastic Syndromes/*genetics/*metabolism/pathology
MH  - *Myelopoiesis
MH  - *Transcription Factor 4/genetics/metabolism
EDAT- 2018/10/14 06:00
MHDA- 2019/03/27 06:00
CRDT- 2018/10/14 06:00
PHST- 2018/06/18 00:00 [received]
PHST- 2018/09/27 00:00 [revised]
PHST- 2018/10/05 00:00 [accepted]
PHST- 2018/10/14 06:00 [pubmed]
PHST- 2019/03/27 06:00 [medline]
PHST- 2018/10/14 06:00 [entrez]
AID - S0301-472X(18)30858-0 [pii]
AID - 10.1016/j.exphem.2018.10.002 [doi]
PST - ppublish
SO  - Exp Hematol. 2019 Jan;69:17-21.e1. doi: 10.1016/j.exphem.2018.10.002. Epub 2018 
      Oct 10.