PMID- 21237204
OWN - NLM
STAT- MEDLINE
DCOM- 20110701
LR  - 20161125
IS  - 1879-0542 (Electronic)
IS  - 0165-2478 (Linking)
VI  - 136
IP  - 1
DP  - 2011 Apr 30
TI  - Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell 
      differentiation from murine hematopoietic stem/progenitor cells.
PG  - 61-73
LID - 10.1016/j.imlet.2010.12.006 [doi]
AB  - Dendritic cells (DCs) play important roles in tumor immunology. Leukemic cells in 
      patients with myeloid neoplasms can differentiate into DCs in vivo (referred to 
      as in vivo leukemic DCs), which are postulated to affect anti-leukemia immune 
      responses. We established a reproducible culture system of in vitro FLT3 
      ligand-mediated DC (FL-DC) differentiation from murine lineage(-) Sca-1(+) 
      c-Kit(high) cells (LSKs), which made it possible to analyse the effects of target 
      genes on steady-state DC differentiation from hematopoietic stem/progenitor 
      cells. Using this system, we analysed the effects of various myeloid 
      neoplasm-related gene abnormalities, termed class I and class II mutations, on 
      FL-DC differentiation from LSKs. All class II mutations uniformly impaired FL-DC 
      differentiation maintaining a plasmacytoid DC (pDC)/conventional DC (cDC) ratio 
      comparable to the control cells. In contrast, class I mutations differentially 
      affected FL-DC differentiation from LSKs. FLT3-ITD and a constitutively active 
      form of Ras (CA-N-Ras) yielded more FL-DCs than the control, whereas the other 
      class I mutations tested yielded less FL-DCs. Both FLT3-ITD and FLT3-tyrosine 
      kinase domain (TKD) mutation showed a comparable pDC/cDC ratio as the control. 
      CA-N-Ras, c-Kit-TKD, TEL/PDGFRbeta, and FIP1L1/PDGFRalpha showed a severe decrease in 
      the pDC/cDC ratio. CA-STAT5 and CA-MEK1 severely inhibited pDC differentiation. 
      FLT3-ITD, CA-N-Ras, and TEL/PDGFRbeta aberrantly induced programmed death ligand-1 
      (PD-L1)-expressing DCs. In conclusion, we have established a simple, efficient, 
      and reproducible in vitro FL-DC differentiation system from LSKs. This system 
      could uncover novel findings on how myeloid neoplasm-related gene abnormalities 
      differentially affect FL-DC differentiation from murine hematopoietic 
      stem/progenitor cells in a gene-specific manner.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Fujita, Jiro
AU  - Fujita J
AD  - Department of Hematology and Oncology, Osaka University Graduate School of 
      Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Mizuki, Masao
AU  - Mizuki M
FAU - Otsuka, Masayasu
AU  - Otsuka M
FAU - Ezoe, Sachiko
AU  - Ezoe S
FAU - Tanaka, Hirokazu
AU  - Tanaka H
FAU - Satoh, Yusuke
AU  - Satoh Y
FAU - Fukushima, Kentaro
AU  - Fukushima K
FAU - Tokunaga, Masahiro
AU  - Tokunaga M
FAU - Matsumura, Itaru
AU  - Matsumura I
FAU - Kanakura, Yuzuru
AU  - Kanakura Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110113
PL  - Netherlands
TA  - Immunol Lett
JT  - Immunology letters
JID - 7910006
RN  - 0 (Antigens, Ly)
RN  - 0 (Ly6a protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (STAT5 Transcription Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens, Ly/immunology
MH  - *Cell Differentiation
MH  - Cell Lineage
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*cytology/*immunology
MH  - Hematopoietic Stem Cells/*cytology/*immunology
MH  - Humans
MH  - MAP Kinase Kinase 1/immunology
MH  - Membrane Proteins/immunology
MH  - Mice
MH  - Multiple Myeloma/*genetics/immunology
MH  - Proto-Oncogene Proteins c-kit/immunology
MH  - STAT5 Transcription Factor/immunology
EDAT- 2011/01/18 06:00
MHDA- 2011/07/02 06:00
CRDT- 2011/01/18 06:00
PHST- 2010/06/07 00:00 [received]
PHST- 2010/12/06 00:00 [revised]
PHST- 2010/12/22 00:00 [accepted]
PHST- 2011/01/18 06:00 [entrez]
PHST- 2011/01/18 06:00 [pubmed]
PHST- 2011/07/02 06:00 [medline]
AID - S0165-2478(11)00002-2 [pii]
AID - 10.1016/j.imlet.2010.12.006 [doi]
PST - ppublish
SO  - Immunol Lett. 2011 Apr 30;136(1):61-73. doi: 10.1016/j.imlet.2010.12.006. Epub 
      2011 Jan 13.