Houwerzijl E J, Blom N R, van der Want J J L, Vellenga E, de Wolf J T M
Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands.
Leukemia. 2006 Nov;20(11):1937-42. doi: 10.1038/sj.leu.2404385. Epub 2006 Sep 7.
Platelet production requires compartmentalized caspase activation within megakaryocytes. This eventually results in platelet release in conjunction with apoptosis of the remaining megakaryocyte. Recent studies have indicated that in low-risk myelodysplastic syndromes (MDS) and idiopathic thrombocytopenic purpura (ITP), premature cell death of megakaryocytes may contribute to thrombocytopenia. Different cell death patterns have been identified in megakaryocytes in these disorders. Growing evidence suggests that, besides apoptosis, necrosis and autophagic cell death, may also be programmed. Therefore, programmed cell death (PCD) can be classified in apoptosis, a caspase-dependent process, apoptosis-like, autophagic and necrosis-like PCD, which are predominantly caspase-independent processes. In MDS, megakaryocytes show features of necrosis-like PCD, whereas ITP megakaryocytes demonstrate predominantly characteristics of apoptosis-like PCD (para-apoptosis). Triggers for these death pathways are largely unknown. In MDS, the interaction of Fas/Fas-ligand might be of importance, whereas in ITP antiplatelet autoantibodies recognizing common antigens on megakaryocytes and platelets might be involved. These findings illustrate that cellular death pathways in megakaryocytes are recruited in both physiological and pathological settings, and that different forms of cell death can occur in the same cell depending on the stimulus and the cellular context. Elucidation of the underlying mechanisms might lead to novel therapeutic interventions.
血小板生成需要巨核细胞内进行分隔的半胱天冬酶激活。这最终会导致血小板释放，并伴随剩余巨核细胞的凋亡。最近的研究表明，在低危骨髓增生异常综合征（MDS）和特发性血小板减少性紫癜（ITP）中，巨核细胞的过早细胞死亡可能导致血小板减少。在这些疾病的巨核细胞中已发现不同的细胞死亡模式。越来越多的证据表明，除了凋亡外，坏死和自噬性细胞死亡也可能是程序性的。因此，程序性细胞死亡（PCD）可分为凋亡（一种半胱天冬酶依赖性过程）、凋亡样、自噬性和坏死样PCD，其中凋亡样、自噬性和坏死样PCD主要是半胱天冬酶非依赖性过程。在MDS中巨核细胞表现出坏死样PCD的特征，而ITP巨核细胞主要表现出凋亡样PCD（副凋亡）的特征。这些死亡途径的触发因素大多未知。在MDS中，Fas/Fas配体的相互作用可能很重要，而在ITP中，识别巨核细胞和血小板上共同抗原的抗血小板自身抗体可能参与其中。这些发现表明，巨核细胞中的细胞死亡途径在生理和病理情况下都会被激活，并且根据刺激和细胞环境的不同，同一细胞中可能会发生不同形式的细胞死亡。阐明其潜在机制可能会带来新的治疗干预措施。
