The bone marrow microenvironment as a sanctuary for minimal residual disease in CML.
The bone marrow microenvironment as a sanctuary for minimal residual disease in CML.
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DOI：
10.1016/j.bcp.2010.04.003
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发表时间：
2010-09-01
影响因子：
5.8
通讯作者：
Hazlehurst LA
中科院分区：
文献类型：
--
作者：
Nair RR;Tolentino J;Hazlehurst LA
Bcr-abl激酶抑制剂为靶向治疗癌症提供了重要证据。然而，尽管这些药物在治疗慢性粒细胞白血病（CML）方面取得了成功，但大多数患者仍存在骨髓微环境中的微小残留疾病。这些临床观察结果表明，骨髓微环境可能提供生存信号，导致无法消除微小残留病变。骨髓微环境由多个子域组成，这些子域在细胞组成和可溶性因子和基质组成的梯度方面不同。实验证据表明，肿瘤细胞暴露于骨髓源性可溶性因子或基质可赋予多药耐药表型。总之，这些数据表明，靶向这些途径可能是提高化疗疗效的可行方法。此外，我们建议个性化医疗必须超越对肿瘤固有的预测模型的理解，而是建立考虑到与肿瘤微环境相互作用的反应多样性的预测模型。本综述将重点关注CML，然而，了解骨髓微环境的贡献可能有助于其他类型的白血病，多发性骨髓瘤和转移到骨的实体瘤的合理联合治疗。
Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the bone marrow microenvironment. These clinical observations suggest that the bone marrow microenvironment may provide survival signals that contribute to the failure to eliminate minimal residual disease. The bone marrow microenvironment is comprised of multiple sub-domains which vary in cellular composition and gradients of soluble factors and matrix composition. Experimental evidence indicates that exposure of tumor cells to either bone marrow derived soluble factors or matrixes can confer a multi-drug resistance phenotype. Together, these data indicate that targeting such pathways may be a viable approach for increasing the efficacy of chemotherapy. Moreover, we propose that personalized medicine must go beyond understanding predictive models inherent to tumors but rather build predictive models that consider diversity in response due to interactions with the tumor microenvironment. This review will focus on CML, however, understanding the contribution of the bone marrow microenvironment could contribute to rationale combination therapy in other types of leukemia, multiple myeloma and solid tumors which metastasize to the bone.
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影响因子：
20.3
作者：
BHATIA, R;MCGLAVE, PB;VERFAILLIE, CM
通讯作者：
VERFAILLIE, CM
DOI：
10.1111/j.1749-6632.1995.tb31044.x
发表时间：
1995-01-01
期刊：
BONE MARROW TRANSPLANTATION: FOUNDATIONS FOR THE 21ST CENTURY
影响因子：
--
作者：
Clark, BR;Keating, A
通讯作者：
Keating, A
影响因子：
11.4
作者：
Brendel, C.;Scharenberg, C.;Neubauer, A.
通讯作者：
Neubauer, A.
影响因子：
6.5
作者：
Angstreich, GR;Matsui, W;Jones, RJ
通讯作者：
Jones, RJ
影响因子：
64.8
作者：
Baggiolini, M
通讯作者：
Baggiolini, M