Department of Pathology and Cancer Center, University of New Mexico, Albuquerque, NM 87131, United States.
Med Hypotheses. 2011 Dec;77(6):1111-3. doi: 10.1016/j.mehy.2011.09.015. Epub 2011 Oct 2.
Multiple hematological side effects have been reported to result from treatment with psychoactive phenothiazines. These reported toxicities include leucopenia, granulocytopenia, thrombocytopenia, agranulocytosis, and bone marrow aplasia. The physiological mechanism causing these potentially life-threatening blood dyscrasias is unknown. Recently, we discovered that phenothiazines exhibit antagonistic properties towards the VLA-4 integrin, an adhesion molecule that is responsible for homing and retention of hematological stem/progenitor cells (HSPCs) in the bone marrow. After administration of thioridazine we detected rapid mobilization of HSPCs into the peripheral blood. We propose that in patients receiving phenothiazines over a prolonged time period, continuous mobilization of stem cells out of the stem cell niche, results in a disorder of hematopoiesis. Furthermore, we also postulate that such cytopenias are caused by a loss of the niche environment, which is known to be essential for stem cell maintenance.
已有报道称，使用具有精神活性的吩噻嗪类药物治疗会导致多种血液学副作用。这些已报道的毒性包括白细胞减少症、粒细胞减少症、血小板减少症、粒细胞缺乏症和骨髓发育不良。导致这些潜在危及生命的血液疾病的生理机制尚不清楚。最近，我们发现吩噻嗪类药物对 VLA-4 整合素具有拮抗作用，VLA-4 整合素是一种黏附分子，负责血液祖细胞（HSPC）归巢和保留在骨髓中。给予硫利达嗪后，我们检测到 HSPC 迅速动员到外周血中。我们提出，在接受吩噻嗪类药物治疗的患者中，干细胞持续从干细胞龛中动员出来，导致造血紊乱。此外，我们还假设这种血细胞减少症是由龛环境丧失引起的，已知龛环境对干细胞维持至关重要。
