Hino K, Nakamaki T
Department of Hematology, Showa University School of Medicine.
Rinsho Ketsueki. 1996 Sep;37(9):770-6.
The mechanism of the cause of hyperleukocytosis induced by differntiation induction therapy of acute promyelocytic leukemia (APL) by all-trans retinoic acid (ATRA) was studies. Of 11 patients treated by ATRA in our hospital, 3 developed hyperleukocytosis. Moreover, 2 out of 4 patients with retinoic acid syndrome (ATRA syndrome) had hyperleukocytosis. Using the patients' leukemia cells as test material, we obteined the following results. In the presence of ATRA at a concentration that induced differentiation in vitro, promotion or supression of differentiation and lineage determination during the differentiation of APL cells involved factors other than ATRA, such as cytokines. Moreover, APL cells that differentiated into monocytoid cells possessed the capability of producing endogenous cytokines such as TNF alpha, which might be involved in the development of ATRA syndrome. Compared to cells from patients without hyperleukocytosis they had a stronger TNF alpha producing capability and lower sensitivity to TGF beta, showing hyperdifferentiation in response to ATRA. Depending on the case, those with the same sensitivity to ATRA might show different sensitivities to cytokines.
对全反式维甲酸（ATRA）诱导分化治疗急性早幼粒细胞白血病（APL）所致高白细胞血症的发病机制进行了研究。在我院接受ATRA治疗的11例患者中，有3例发生了高白细胞血症。此外，在4例维甲酸综合征（ATRA综合征）患者中，有2例出现了高白细胞血症。以患者的白血病细胞作为检测材料，我们获得了以下结果。在体外诱导分化的ATRA浓度存在的情况下，APL细胞分化过程中的分化促进或抑制以及谱系确定涉及ATRA以外的其他因素，如细胞因子。此外，分化为单核细胞样细胞的APL细胞具有产生内源性细胞因子如TNFα的能力，这可能与ATRA综合征的发生有关。与无高白细胞血症患者的细胞相比，它们具有更强的TNFα产生能力和对TGFβ的较低敏感性，显示出对ATRA的过度分化。根据具体情况，对ATRA敏感性相同的患者对细胞因子可能表现出不同的敏感性。
