Biology of chronic lymphocytic leukemia in different microenvironments: clinical and therapeutic implications.
Biology of chronic lymphocytic leukemia in different microenvironments: clinical and therapeutic implications.
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DOI：
10.1016/j.hoc.2013.01.002
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发表时间：
2013-04
影响因子：
2.4
通讯作者：
Wiestner, Adrian
中科院分区：
文献类型：
--
作者：
Herishanu, Yair;Katz, Ben-Zion;Lipsky, Andrew;Wiestner, Adrian
慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病。CLL通常是一种惰性淋巴细胞增生性疾病，其特征是外周血、骨髓和次级淋巴器官中单克隆、小的、成熟的CD5+ b细胞的进行性积累除了同种异体干细胞移植外，CLL目前是一种无法治愈的疾病，尽管化疗免疫治疗获得了良好的初始反应，延长了总生存期目前的治疗方式似乎在根除骨髓和淋巴结中的恶性CLL细胞方面不如在外周血中有效。因此，最初获得缓解的患者最终会出现复发性疾病。此外，该疾病在不同解剖位置的差异反应表明，组织微环境在支持CLL细胞存活并使其逃避化疗毒性作用方面发挥了重要作用。最近的研究表明，CLL细胞的运输、存活和增殖受到周围组织微环境的严格调控（图1）。这一结论得到了几方面证据的支持。在体外培养时，CLL细胞迅速发生凋亡，但它们可以通过与基质细胞接触暂时从程序性细胞死亡中获救。基质细胞也被认为对化疗诱导的细胞凋亡具有保护作用。[3,4]此外，CLL细胞在不同组织间室中的特征也存在差异。外周血中的CLL细胞停留在细胞周期的G0/G1期[5]，并表现出与程序性细胞死亡缺陷和体内生存期延长[5]一致的特征。以前，这一观察结果被认为表明CLL是一种静止的非增殖细胞的恶性肿瘤。然而，最近关于端粒长度[6]和CLL细胞动力学体内测量的数据表明，CLL细胞的更新比
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. An often indolent lymphoproliferative disorder, CLL is characterized by the progressive accumulation of monoclonal, small, mature-appearing CD5+ B-cells in the peripheral blood, bone marrow and secondary lymphoid organs.[1] With the notable exception of allogeneic stem cell transplantation, CLL is currently an incurable disease, despite the fact that good initial responses to chemoimmunotherapy are obtained, which prolong overall survival.[2] Current treatment modalities appear to eradicate malignant CLL cells less efficiently in the bone marrow and lymph nodes than in peripheral blood. Thus, patients who initially achieve a remission will eventually develop recurrent disease. Moreover, the differential response of the disease in different anatomic locations indicates a significant role of the tissue microenvironment in supporting CLL cell survival and enabling them to evade the toxic effects of chemotherapy.Recent work has demonstrated that the trafficking, survival and proliferation of CLL cells is tightly regulated by the surrounding tissue microenvironment (Figure 1). This conclusion is bolstered by several lines of evidence. When cultured in vitro, CLL cells rapidly undergo apoptosis, but they can be temporarily rescued from programmed cell death by contact with stromal cells. Stromal cells are also known to confer a protective effect against chemotherapy-induced apoptosis.[3, 4] Additionally, there are differences in the characteristics of CLL cells in the various tissue compartments. CLL cells in the peripheral blood are arrested in G0/G1 phase of the cell cycle [5] and display features that are consistent with a defect in programmed cell death and prolonged in vivo survival [1]. Previously, this observation was thought to suggest that CLL is a malignancy of quiescent non-proliferating cells. However, recent data on telomere length [6] and in vivo measurement of CLL cell kinetics demonstrated that CLL cells exhibit a more prominent turnover than
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1158/1078-0432.ccr-10-2879
发表时间：
2011-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Amrein PC;Attar EC;Takvorian T;Hochberg EP;Ballen KK;Leahy KM;Fisher DC;Lacasce AS;Jacobsen ED;Armand P;Hasserjian RP;Werner L;Neuberg D;Brown JR
通讯作者：
Brown JR
影响因子：
20.3
作者：
Bagnara, Davide;Kaufman, Matthew S.;Chiorazzi, Nicholas
通讯作者：
Chiorazzi, Nicholas
DOI：
10.3324/haematol.2009.005835
发表时间：
2009-09-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Aue, Georg;Njuguna, Ndegwa;Wiestner, Adrian
通讯作者：
Wiestner, Adrian
影响因子：
20.3
作者：
Buerkle, Andrea;Niedermeier, Matthias;Burger, Jan A.
通讯作者：
Burger, Jan A.