Circulating myeloid dendritic cell directly isolated from patients with chronic myelogenous leukemia are functional and carry the bcr-abl translocation

被引:11
作者
Orsini, Enrica [1 ]
Calabrese, Elisabetta [1 ]
Maggio, Roberta [1 ]
Pasquale, Alessia [1 ]
Nanni, Mauro [1 ]
Trasarti, Stefania [1 ]
Tafuri, Agostino [1 ]
Guarini, Anna [1 ]
Foa, Robert [1 ]
机构
[1] Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, I-00161 Rome, Italy
关键词
dendritic cells; chronic myelogenous leukemia; bcr-abl; T cells; costimulatory molecules;
D O I
10.1016/j.leukres.2005.11.028
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Leukemic bcr-abl positive dendritic cells (DCs) are likely to be present in vivo in chronic myelogenous leukemia (CML) patients, but no data are available on their functional qualities. We analyzed the circulating BDCA-1+ myeloid DC compartment in 15 chronic phase CML patients. Phenotypic features of CML DCs were comparable with that of normal DCs, except for the CD80 and CD40 antigens, significantly under-represented in CML patients. Nonetheless, no differences were found between normal samples and leukemic DCs in the allostimulatory ability, as well as in the production of cytokines and polarization of T cell responses. CML DCs were analyzed by fluorescence in situ hybridization (FISH) and found positive for the bcr-abl translocation. However, when bcr-abl+ DCs were tested for their ability to stimulate an autologous T-cell response in vitro, we could not detect a specific recognition. We conclude that an apparently normal circulating DC compartment carrying the Ph+ chromosome can be identified in CML patients; however, these cells appear unable to trigger a protective anti-leukemic immune response in autologous T cells. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:785 / 794
页数:10
相关论文
共 55 条
[1]  
Almand B, 2000, CLIN CANCER RES, V6, P1755
[2]   Origin and differentiation of dendritic cells [J].
Ardavín, C ;
del Hoyo, GM ;
Martín, P ;
Anjuère, F ;
Arias, CF ;
Marín, AR ;
Ruiz, S ;
Parrillas, V ;
Hernández, H .
TRENDS IN IMMUNOLOGY, 2001, 22 (12) :691-700
[3]   DETECTION OF THE PHILADELPHIA-CHROMOSOME IN INTERPHASE NUCLEI [J].
ARNOLDUS, EPJ ;
WIEGANT, J ;
NOORDERMEER, IA ;
WESSELS, JW ;
BEVERSTOCK, GC ;
GROSVELD, GC ;
VANDERPLOEG, M ;
RAAP, AK .
CYTOGENETICS AND CELL GENETICS, 1990, 54 (3-4) :108-&
[4]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[5]   THE CHRONIC MYELOGENOUS LEUKEMIA SPECIFIC P210-PROTEIN IS THE PRODUCT OF THE BCR/ABL HYBRID GENE [J].
BEN-NERIAH, Y ;
DALEY, GQ ;
MESMASSON, AM ;
WITTE, ON ;
BALTIMORE, D .
SCIENCE, 1986, 233 (4760) :212-214
[6]  
Bertazzoli C, 2000, CLIN CANCER RES, V6, P1931
[7]  
Bocchia M, 2005, LANCET, V365, P657
[8]   Specific human cellular immunity to bcr-abl oncogene-derived peptides [J].
Bocchia, M ;
Korontsvit, T ;
Xu, Q ;
Mackinnon, S ;
Yang, SY ;
Sette, A ;
Scheinberg, DA .
BLOOD, 1996, 87 (09) :3587-3592
[9]   B7 BUT NOT INTERCELLULAR-ADHESION MOLECULE-1 COSTIMULATION PREVENTS THE INDUCTION OF HUMAN ALLOANTIGEN-SPECIFIC TOLERANCE [J].
BOUSSIOTIS, VA ;
FREEMAN, GJ ;
GRAY, G ;
GRIBBEN, J ;
NADLER, LM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (05) :1753-1763
[10]   Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-β1 and interleukin-10 [J].
Brown, RD ;
Pope, B ;
Murray, A ;
Esdale, W ;
Sze, DM ;
Gibson, J ;
Ho, PJ ;
Hart, D ;
Joshua, D .
BLOOD, 2001, 98 (10) :2992-2998