Imatinib and plasmacytoid dendritic cell function in patients with chronic myeloid leukemia
Imatinib and plasmacytoid dendritic cell function in patients with chronic myeloid leukemia
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DOI：
10.1182/blood-2003-09-3220
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发表时间：
2004-06-15
期刊：
影响因子：
20.3
通讯作者：
Gaugler, B
中科院分区：
文献类型：
--
作者：
Mohty, M;Jourdan, E;Gaugler, B
浆细胞样树突状细胞（PDCs）是先天免疫中的重要效应细胞。在这项研究中，我们发现，伊马替尼，一个有效的抑制剂BCR/ABL酪氨酸激酶活性，在Flt 3-配体的存在下，可以诱导CD 34（+）的祖细胞从慢性粒细胞白血病（CML）在体外产生典型的BDCA-2（+）I型干扰素生产PDCs。伊马替尼对PDC生成的影响与白血病CD 34（+）祖细胞上Flt 3的上调有关。此外，伊马替尼治疗后完全细胞遗传学或分子反应的慢性粒细胞白血病（CML）患者在定量和功能上恢复了与健康供体相当的血液PDCs。与对伊马替尼无应答的患者相反，进一步证实了对伊马替尼的疾病应答伴随着体内PDC功能的恢复。这些发现提供了证据表明，对伊马替尼的反应能够恢复CML中一些DC相关的免疫功能，这可能有利于长期疾病控制。(C)2004年，美国血液学会。
Plasmacytoid dendritic cells (PDCs) are crucial effectors in innate immunity. In this study, we show that imatinib, a potent inhibitor of BCR/ABL tyrosine kinase activity, in the presence of Flt3-Ligand, could induce CD34(+) progenitors from chronic myeloid leukemia (CML) to give rise in vitro to typical BDCA-2(+) type I interferon-producing PDC.s. The effect of imatinib on PDC generation was related to up-regulation; of Flt3 on leukemic CD34(+) progenitors. Moreover, patients with chronic myeloid leukemia (CML) who were in complete cytogenetic or molecular response after imatinib treatment restored their blood PDCs both quantitatively and functionally comparable to healthy donors, in. contrast to patients not responding to imatinib, further confirming that disease response to imatinib is accompanied by restoration of PDC function in vivo. These findings provide evidence that response to imatinib is capable to restore some DC-related immune functions in CML that might be beneficial for long-term disease control. (C) 2004 by The American Society of Hematology.