Circulating blood dendritic cells from myeloid leukemia patients display quantitative and cytogenetic abnormalities as well as functional impairment

被引:148
作者
Mohty, M
Jarrossay, D
Lafage-Pochitaloff, M
Zandotti, C
Brière, F
de Lamballeri, XN
Isnardon, D
Sainty, D
Olive, D
Gaugler, B
机构
[1] Univ Mediterranee, Inst J Paoli I Calmettes, Lab Immunol Tumeurs, F-13273 Marseille 09, France
[2] Univ Mediterranee, Inst J Paoli I Calmettes, Lab Cytogenet, F-13273 Marseille 09, France
[3] Univ Mediterranee, Inst J Paoli I Calmettes, Dept Hematol, F-13273 Marseille 09, France
[4] Immunotech SA, Marseille, France
[5] Beckman Coulter, Marseille, France
[6] Hop Enfants La Timone, Virol Lab, F-13385 Marseille, France
[7] INSERM, U119, F-13258 Marseille, France
[8] Schering Plough Corp, Lab Immunol Res, Dardilly, France
关键词
D O I
10.1182/blood.V98.13.3750
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Dendritic cells (DCs) are responsible for the initiation of immune responses. Two distinct subsets of blood DCs have been characterized thus far. Myeloid DCs (MDCs) and plasmacytoid monocytes (PDCs) were shown to be able to promote polarization of naive T cells. This study shows a dramatic quantitative imbalance in both circulating blood DC subsets in 37 patients with acute myeloid leukemias. Eleven patients (30%) displayed a normal quantitative profile (MDC mean, 0.37% +/- 0.21%; range, 0.01% to 0.78%; PDC mean, 0.21% +/- 0.24%; range, 0.04% to 0.62%), whereas 22 (59%) showed a tremendous expansion of MDCs (9 patients: mean, 16.76% +/- 14.03%; range, 1.36% to 41%), PDCs (4 patients: mean, 7.28% +/- 6.84%; range, 1% to 14%), or both subsets (9 patients: MDC mean, 10.86% +/- 12.36%; range, 1.02% to 37.1%; PDC mean, 4.25% +/- 3.78%; range, 1.14% to 13.04%). Finally, in 4 patients (11%), no DC subsets were detectable. Both MDC and PDC subsets exhibited the original leukemic chromosomal abnormality. Ex vivo, leukemic PDCs, but not leukemic MDCs, had Impaired capacity for maturation and decreased allostimulatory, activity. Also, leukemic PDCs were altered in their ability to secrete interferon-alpha. These data provide evidence that DC subsets in vivo may be affected by leukemogenesis and may contribute to leukemia escape from Immune control. (C) 2001 by The American Society of Hematology.
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收藏
页码:3750 / 3756
页数:7
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