PMID- 12506035
OWN - NLM
STAT- MEDLINE
DCOM- 20030620
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 9
DP  - 2003 May 1
TI  - Dendritic cells from CML patients have altered actin organization, reduced 
      antigen processing, and impaired migration.
PG  - 3560-7
AB  - Chronic myeloid leukemia (CML) is characterized by expression of the BCR-ABL 
      fusion gene that encodes a 210-kDa protein, which is a constitutively active 
      tyrosine kinase. At least 70% of the oncoprotein is localized to the 
      cytoskeleton, and several of the most prominent tyrosine kinase substrates for 
      p210(BCR-ABL) are cytoskeletal proteins. Dendritic cells (DCs) are bone 
      marrow-derived antigen-presenting cells responsible for the initiation of immune 
      responses. In CML patients, up to 98% of myeloid DCs generated from peripheral 
      blood mononuclear cells are BCR-ABL positive. In this study we have compared the 
      morphology and behavior of myeloid DCs derived from CML patients with control DCs 
      from healthy individuals. We show that the actin cytoskeleton and shape of 
      CML-DCs of myeloid origin adherent to fibronectin differ significantly from those 
      of normal DCs. CML-DCs are also defective in processing and presentation of 
      exogenous antigens such as tetanus toxoid. The antigen-processing defect may be a 
      consequence of the reduced capacity of CML-DCs to capture antigen via 
      macropinocytosis or via mannose receptors when compared with DCs generated from 
      healthy individuals. Furthermore, chemokine-induced migration of CML-DCs in vitro 
      was significantly reduced. These observations cannot be explained by a difference 
      in the maturation status of CML and normal DCs, because phenotypic analysis by 
      flow cytometry showed a similar surface expression of maturation makers. Taken 
      together, these results suggest that the defects in antigen processing and 
      migration we have observed in CML-DCs may be related to underlying cytoskeletal 
      changes induced by the p210(BCR-ABL) fusion protein.
FAU - Dong, Rong
AU  - Dong R
AD  - Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial 
      College at Hammersmith Hospital, London, United Kingdom.
FAU - Cwynarski, Kate
AU  - Cwynarski K
FAU - Entwistle, Alan
AU  - Entwistle A
FAU - Marelli-Berg, Federica
AU  - Marelli-Berg F
FAU - Dazzi, Francesco
AU  - Dazzi F
FAU - Simpson, Elizabeth
AU  - Simpson E
FAU - Goldman, John M
AU  - Goldman JM
FAU - Melo, Junia V
AU  - Melo JV
FAU - Lechler, Robert I
AU  - Lechler RI
FAU - Bellantuono, Ilaria
AU  - Bellantuono I
FAU - Ridley, Anne
AU  - Ridley A
FAU - Lombardi, Giovanna
AU  - Lombardi G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20021227
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Actins)
RN  - 0 (Fibronectins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Tetanus Toxoid)
SB  - IM
MH  - Actin Cytoskeleton/*ultrastructure
MH  - Actins/*analysis
MH  - Adolescent
MH  - Adult
MH  - *Antigen Presentation
MH  - Cell Adhesion
MH  - Cells, Cultured/drug effects/immunology/pathology
MH  - Chemotaxis
MH  - Cytoskeleton/*ultrastructure
MH  - Dendritic Cells/immunology/*pathology
MH  - Endocytosis
MH  - Fibronectins
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lectins, C-Type
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*immunology/pathology
MH  - Lymphocyte Activation
MH  - Mannose Receptor
MH  - *Mannose-Binding Lectins
MH  - Microscopy, Confocal
MH  - Monocytes/drug effects
MH  - Neoplasm Proteins/physiology
MH  - Pinocytosis
MH  - Receptors, Cell Surface/physiology
MH  - T-Lymphocyte Subsets/immunology
MH  - Tetanus Toxoid/immunology
EDAT- 2002/12/31 04:00
MHDA- 2003/06/21 05:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/06/21 05:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S0006-4971(20)50738-6 [pii]
AID - 10.1182/blood-2002-06-1841 [doi]
PST - ppublish
SO  - Blood. 2003 May 1;101(9):3560-7. doi: 10.1182/blood-2002-06-1841. Epub 2002 Dec 
      27.