Contribution of Nitric Oxide to the Apoptotic Process in Human B Cell Chronic Lymphocytic Leukaemia
Contribution of Nitric Oxide to the Apoptotic Process in Human B Cell Chronic Lymphocytic Leukaemia
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DOI：
10.3109/10428190109057923
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发表时间：
2001-01
影响因子：
2.6
通讯作者：
J. Kolb;V. Roman;F. Mentz;Haixia Zhao;D. Rouillard;N. Dugas;B. Dugas;F. Sigaux
中科院分区：
文献类型：
--
作者：
J. Kolb;V. Roman;F. Mentz;Haixia Zhao;D. Rouillard;N. Dugas;B. Dugas;F. Sigaux
B细胞慢性淋巴细胞白血病（B- cll）的特征是细胞凋亡缺陷，不能仅仅根据已知的染色体异常来解释。我们和其他人现在已经报道了白血病细胞自发地显示一氧化氮合酶的诱导异构体，iNOS。体外实验表明，抑制iNOS通路导致肿瘤细胞凋亡增加，表明NO的内源性释放有助于肿瘤细胞抵抗正常的凋亡过程。在白血病细胞体内诱导iNOS表达的因素尚未确定。然而，由于B-CLL白血病细胞与骨髓基质细胞的相互作用促进了它们的存活，因此可能怀疑粘附分子和整合素的参与。CD23的参与刺激肿瘤细胞中的iNOS激活，表明CD23与其识别的一种配体的体内相互作用可能有助于诱导iNOS。也可以假设CD40-CD40配体相互作用的作用。NO抗凋亡作用的机制尚不完全清楚，但可能涉及抑制caspase活性，从而损害Fas途径。此外，线粒体膜电位破坏似乎是凋亡级联过程中no敏感的一步。NOS具有抗凋亡特性，现已在包括各种白血病在内的不同细胞类型中得到证实。更好地了解NO的最终命运，抗凋亡与促凋亡的机制将允许开发新的治疗方法来治疗这些疾病。
B cell chronic lymphocytic leukaemia (B-CLL) is characterised by defective apoptosis that cannot be explained solely on the basis of the known chromosomal abnormalities. We and other have now reported that the leukemic cells spontaneously display the inducible isoform of nitric oxide synthase, iNOS. Inhibition of the iNOS pathway leads to increased apoptosis of the tumoral cells in vitro, indicating that the endogenous release of NO contributes to their resistance to the normal apoptotic process. The factors that induce the expression of iNOS in vivo in the leukemic cells are not yet identified. Yet, as interaction of B-CLL leukemic cells with bone marrow stromal cells promotes their survival, the involvement of adhesion molecules and integrins may be suspected. The engagement of CD23 stimulates iNOS activation in the tumoral cells, suggesting that in vivo interaction of CD23 with one of its recognised lig-ands may contribute to iNOS induction. A role for CD40-CD40 ligand interaction may also be hypothesised. The mechanisms involved in the anti-apoptotic role of NO are not fully understood, but may implicate the inhibition of caspase activity, hence the impairment of the Fas pathway. In addition, the mitochondrial membrane potential disruption appears to be a NO-sensitive step in the apoptosis cascade. The presence of a NOS displaying anti-apoptotic properties has now been recognised in different cell types, including various leukaemia. A better knowledge of the mechanisms governing the ultimate fate of NO, anti-versus pro-apoptotic would allow the development of new therapeutic approaches for the treatment of these diseases.