Sato Naoko, Narita Miwako, Takahashi Masuhiro, Yagisawa Kumiko, Liu Aichun, Abe Takashi, Nikkuni Kohji, Furukawa Tatsuo, Toba Ken, Aizawa Yoshifusa
First Department of Internal Medicine, Niigata University School of Medicine, Niigata City, Japan.
Hematol Oncol. 2003 Jun;21(2):67-75. doi: 10.1002/hon.705.
Chronic myelogenous leukemia is caused by the acquisition of the reciprocal (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion protein showed higher and aberrant tyrosine kinase activity. The inhibition of the tyrosine kinase activity of the protein represents a specific therapeutic strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the Abl protein tyrosine kinase. In this study, we evaluated the effects of STI571 on antigen presentation of dendritic cells generated from the patients with CML. The data showed that by the addition of STI571 the dendritic cells derived from CML clone showed an increased expression of CD1a, CD83, CD80 and CD86 by flow cytometry analysis and showed more intense abilities of allogeneic antigen presentation by mixed leukocyte culture, compared with the control cells without STI571. Our results suggested that STI571 not only has a direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect effect associated with increased anti-leukemic immunological function due to an intensified antigen presentation.
慢性粒细胞白血病是由造血干细胞获得相互易位的(9;22)(q34;q11)染色体所致。融合蛋白表现出更高的异常酪氨酸激酶活性。抑制该蛋白的酪氨酸激酶活性是治疗表达bcr/abl的白血病的一种特异性治疗策略。STI571是一种2-苯胺基嘧啶类化合物,可选择性抑制Abl蛋白酪氨酸激酶的酪氨酸激酶活性。在本研究中,我们评估了STI571对慢性粒细胞白血病患者来源的树突状细胞抗原呈递的影响。数据显示,通过流式细胞术分析,添加STI571后,慢性粒细胞白血病克隆来源的树突状细胞CD1a、CD83、CD80和CD86的表达增加,与未添加STI571的对照细胞相比,混合淋巴细胞培养显示出更强的同种异体抗原呈递能力。我们的结果表明,STI571不仅对bcr-abl基因重排细胞有直接细胞毒性作用,而且由于抗原呈递增强,还具有与抗白血病免疫功能增强相关的间接作用。