PMID- 16531819
OWN - NLM
STAT- MEDLINE
DCOM- 20060525
LR  - 20080318
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 29
IP  - 2
DP  - 2006 Mar-Apr
TI  - Constitutively active STAT5b induces cytokine-independent growth of the acute 
      myeloid leukemia-derived MUTZ-3 cell line and accelerates its differentiation 
      into mature dendritic cells.
PG  - 188-200
AB  - The CD34(+) human acute myeloid leukemia-derived cell line MUTZ-3 is dependent on 
      hematopoietic growth factors for its proliferation and is able to differentiate 
      into dendritic cells (DCs) in response to the combination of 
      granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor 
      necrosis factor-alpha. This cell line carries human leukocyte antigen (HLA)-A2.1, 
      HLA-A3, and HLA-B44, which cover most of the caucasian population, and it could 
      therefore be used as an off-the-shelf allogeneic DC-based vaccine. Signal 
      transduction and activation of transcription (STAT) 5b is involved in cytokine 
      signal transduction, particularly of cytokines involved in DC precursor growth 
      and differentiation. The constitutively active form of STAT5b induced 
      cytokine-independent growth of MUTZ-3 cells. Furthermore, STAT5b-transduced cells 
      differentiated into mature DCs in 3 to 4 days after stimulation with DC 
      differentiation-inducing cytokines, reducing the culture period to obtain mature 
      DCs with 5 days compared with unmodified MUTZ-3-derived mature DC cultures. Both 
      DC types expressed DC maturation markers and were equally effective in inducing 
      primary T-cell responses. DCs derived from the STAT5b-transduced cells had a more 
      stable mature phenotype after cytokine deprivation, which was reflected in a 
      better performance in functional assays. In conclusion, these results show that 
      STAT5b-transduced MUTZ-3 can be propagated in cytokine-free medium and rapidly 
      differentiated into functional mature DCs that sustain a mature phenotype over a 
      period of 3 to 5 days in the absence of differentiation-inducing cytokines. The 
      simplified propagation and rapid differentiation into mature DCs may facilitate 
      clinical application of this cell line as an allogeneic DC-based vaccine.
FAU - Bontkes, Hetty J
AU  - Bontkes HJ
AD  - Department of Pathology, Vrije Universiteit University Medical Center, Amsterdam, 
      The Netherlands. hj.bontkes@vumc.nl
FAU - Ruizendaal, Janneke J
AU  - Ruizendaal JJ
FAU - Kramer, Duco
AU  - Kramer D
FAU - Santegoets, Saskia J A M
AU  - Santegoets SJ
FAU - Scheper, Rik J
AU  - Scheper RJ
FAU - de Gruijl, Tanja D
AU  - de Gruijl TD
FAU - Meijer, Chris J L M
AU  - Meijer CJ
FAU - Hooijberg, Erik
AU  - Hooijberg E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, CD)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (STAT5B protein, human)
SB  - IM
MH  - Antigens, CD
MH  - Cancer Vaccines/immunology
MH  - Cell Differentiation/*immunology
MH  - Cell Line, Tumor
MH  - Cytokines/pharmacology
MH  - Dendritic Cells/immunology/metabolism/*pathology
MH  - Gene Expression Regulation, Neoplastic/immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Leukemia, Myeloid, Acute/immunology/metabolism/*pathology
MH  - STAT5 Transcription Factor/genetics/*immunology/metabolism
MH  - Signal Transduction/immunology
EDAT- 2006/03/15 09:00
MHDA- 2006/05/26 09:00
CRDT- 2006/03/15 09:00
PHST- 2006/03/15 09:00 [pubmed]
PHST- 2006/05/26 09:00 [medline]
PHST- 2006/03/15 09:00 [entrez]
AID - 00002371-200603000-00008 [pii]
AID - 10.1097/01.cji.0000197095.00359.67 [doi]
PST - ppublish
SO  - J Immunother. 2006 Mar-Apr;29(2):188-200. doi: 
      10.1097/01.cji.0000197095.00359.67.