Mechanisms of acute promyelocytic leukemia cell infiltration and mobilization during ATRA therapy: new strategy for prevention of ATRA syndrome and additional chemotherapy.

ATRA治疗期间急性早幼粒细胞白血病细胞浸润和动员的机制：预防ATRA综合征和额外化疗的新策略。

• 批准号: 23650603
• 负责人: GOTOU Akihiko
• 金额: $ 1.83万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23650603/
• 关键词: 急性前骨髄性白血病; CXCL12; CXCR4; 走化性; all-trans retinoic acid; CXCR7; phospholipaseC; ATRA

Differentiation-induction therapy with all trans retinoic acid (ATRA) is the first line therapy in acute promyelocytic leukemia (APL). Differentiation syndrome (DS) is the most serious adverse event during ATRA therapy. Further, although mobilization of APL cells into peripheral blood requires additional chemotherapy during ATRA therapy, the mechanism of the mobilization is unclear. In the current study, CXCL12 appeared to be a chemoattractant of APL cells. Treatment of APL cells with ATRA enhanced chmotaxis towards CXCL12. Increase of chemotaxis significantly associated with occurrence of DS and the requirement of additional chemotherapy. Activation of phospholipase C pathway appeared to be crucial for the chemotaxis. These results suggest that chomotaxis ability of APL cells toward CXCL12 is involved in the pathogenesis of DS and the requirement of chemotherapy during induction therapy with ATRA. Furthermore, specific signal targeted-therapy might contribute to prevent DS and additional chemotherapy.

全反式维甲酸（ATRA）诱导分化治疗是急性早幼粒细胞白血病（APL）的一线治疗方法。分化综合征（DS）是ATRA治疗过程中最严重的不良反应。此外，虽然动员APL细胞进入外周血需要额外的化疗ATRA治疗期间，动员的机制尚不清楚。在目前的研究中，CXCL 12似乎是APL细胞的化学引诱物。ATRA处理APL细胞可增强细胞对CXCL 12的趋化性。趋化性的增加与DS的发生和额外化疗的需要显著相关。磷脂酶C途径的激活似乎是趋化性的关键。提示APL细胞对CXCL 12的趋化能力与DS的发病机制及ATRA诱导治疗中化疗的需要有关。此外，特异性信号靶向治疗可能有助于预防DS和额外的化疗。

项目成果

Chemotaxis of acute promyelocytic leukemia cells toward CXCL12 is involved in ATRA syndrome and the requirement of chemotherapy during induction therapy with ATRA

急性早幼粒细胞白血病细胞对CXCL12的趋化性与ATRA综合征有关以及ATRA诱导治疗期间化疗的需要

• 发表时间: 2012
• 作者: 後藤明彦;青田泰雄;宮澤啓介;木崎昌弘;大屋敷一馬
• 通讯作者: 大屋敷一馬

Chemotaxis of acute promyelocytic leukemia cells toward CXCL12 is involved in ATRA syndrome and the requirement of chemotherapy during induction therapy with ATRA.

急性早幼粒细胞白血病细胞对 CXCL12 的趋化性与 ATRA 综合征以及 ATRA 诱导治疗期间化疗的需要有关。

• 发表时间: 2012
• 作者: Gotoh A;Aota Y;Miyazawa K;Kizaki M;Ohyashiki K
• 通讯作者: Ohyashiki K