Department of Neurological Sciences (DNNMMS), University of Verona, Verona, Italy.
Cell Signal. 2012 Jul;24(7):1433-43. doi: 10.1016/j.cellsig.2012.03.008. Epub 2012 Mar 13.
B-cell chronic lymphocytic leukemia (CLL), which is the most common lymphoproliferative disorder, displays characteristics consistent with a defect in programmed cell death and exhibit prolonged survival of affected cells in vivo. When recovered from peripheral blood or lymphoid tissues of patients and cultured in vitro, CLL malignant cells rapidly undergo spontaneous apoptosis. CLL B-cells co-culture with different adherent cell types, collectively referred to as stromal cells, induces leukemia cell survival, migration, and drug resistance. In addition, such survival-promoting microenvironments can rescue leukemia cells from cytotoxic therapy, giving way to disease relapse. Quite surprisingly considering that many anti-cancer drugs, including γ-secretase inhibitors, Cyclopamine and Quercetin, were reported to block Notch, Wnt, and Hedgehog anti-apoptotic signaling pathways respectively, the link between the latter anti-apoptotic pathways and bone marrow stromal cells in CLL has been pointed out only recently. Data concerning the pathogenesis of CLL have been critically reviewed in regards to the growing body of evidence indicating deregulations of Notch, Wnt and Hedgehog anti-apoptotic signaling pathways in the stromal microenvironment of affected cells.
B 细胞慢性淋巴细胞白血病（CLL）是最常见的淋巴增殖性疾病，其特征与程序性细胞死亡缺陷一致，并表现出体内受影响细胞的存活时间延长。当从患者的外周血或淋巴组织中回收并在体外培养时，CLL 恶性细胞会迅速自发凋亡。CLL B 细胞与不同的贴壁细胞类型共培养，统称为基质细胞，可诱导白血病细胞存活、迁移和耐药。此外，这种促进生存的微环境可以使白血病细胞免受细胞毒性治疗的影响，从而导致疾病复发。令人惊讶的是，尽管许多抗癌药物，包括 γ-分泌酶抑制剂、环巴胺和槲皮素，分别被报道可阻断 Notch、Wnt 和 Hedgehog 抗凋亡信号通路，但直到最近才指出后者的抗凋亡通路与 CLL 中的骨髓基质细胞之间存在联系。有关 CLL 发病机制的研究数据已经受到严格审查，因为越来越多的证据表明 Notch、Wnt 和 Hedgehog 抗凋亡信号通路在受影响细胞的基质微环境中失调。
