PMID- 17895399
OWN - NLM
STAT- MEDLINE
DCOM- 20080219
LR  - 20071224
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 83
IP  - 1
DP  - 2008 Jan
TI  - Aberrant dendritic cell differentiation initiated by the Mll-Een fusion gene does 
      not require leukemic transformation.
PG  - 173-80
AB  - Dendritic cells (DCs), as specialized APCs, play a key role in the induction of 
      anti-tumor immunity. They originate from bone marrow (BM) progenitors, which are 
      frequently the targets of chromosomal translocations leading to development of 
      leukemia. Aberrant DC differentiation and functions have been observed and are 
      widely reported in patients with leukemia. It is not clear, however, whether such 
      defects are a direct effect of a leukemic fusion gene or simply an outcome of the 
      clinical disease. In this study, we demonstrate for the first time that knockin 
      of the Mll-Een fusion gene can affect myeloid DC differentiation and functions 
      directly, independent of the leukemic disease activities. We showed that the 
      Mll-Een-expressing BM cells [enhanced green fluorescent protein+ (EGFP+)] from 
      leukemic and nonleukemic mice had similarly impaired DC differentiation 
      capacities with functional abnormalities. In contrast, BM cells without Mll-Een 
      expression (EGFP(-)) showed normal DC differentiation and functions. A reduction 
      in the frequency of CD11c+ DCs was also observed within the EGFP+ population in 
      spleen and lymph nodes, and these cells were dysfunctional. Taken together, our 
      findings suggest that the Mll-Een fusion gene can affect myeloid DC 
      differentiation directly and functions in a cell-autonomous manner, where fully 
      leukemic transformation of the hematopoietic progenitors is not required 
      exclusively. Therefore, the study provides evidence for a direct causal 
      relationship between leukemic gene fusion and abnormal DC differentiation, 
      possibly contributing to the development of leukemia.
FAU - Sun, Q
AU  - Sun Q
AD  - Department of Pathology, S. H. Ho Foundation research Laboratories, The 
      University of Hong Kong, University Pathology Building, Queen Mary Hospital, 102 
      Pokfulam Road, Pokfulam, Hong Kong, SAR, China.
FAU - Kong, C T
AU  - Kong CT
FAU - Huang, F P
AU  - Huang FP
FAU - Chan, L C
AU  - Chan LC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070925
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Cytokines)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics/immunology
MH  - Cell Movement/immunology
MH  - Cell Transformation, Neoplastic/*genetics/immunology
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*immunology
MH  - Flow Cytometry/methods
MH  - Leukemia/*genetics/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics/metabolism
MH  - T-Lymphocytes/immunology
EDAT- 2007/09/27 09:00
MHDA- 2008/02/20 09:00
CRDT- 2007/09/27 09:00
PHST- 2007/09/27 09:00 [pubmed]
PHST- 2008/02/20 09:00 [medline]
PHST- 2007/09/27 09:00 [entrez]
AID - jlb.0607348 [pii]
AID - 10.1189/jlb.0607348 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2008 Jan;83(1):173-80. doi: 10.1189/jlb.0607348. Epub 2007 Sep 25.