Blood：科学家发现白血病致病蛋白

近日，辛辛那提大学（UC）Hoxworth血液中心研究人员发现治疗白血病的新靶基因。这一研究结果将于7月26日刊登在美国血液学会Blood杂志上。
 
这项研究由在加州大学医学部儿科副教授和Hoxworth血液中心研究部主任Jose Cancelas博士领导，研究团队在动物模型中抑制Vav3蛋白，从而控制细胞信号转导，动物发展患有 BCR-ABL淋巴白血病被延迟。

尽管治疗白血病的治疗手段一直在进步，但BCR-ABL淋巴白血病患者的治疗结果却是非常差的，因为这一类型的白血病易产生耐药性。总之研究发现Vav3蛋白遗传缺陷能控制白血病BCR-ABL的发病。

Cancelas表示：这一发现可能导致新的多靶治疗白血病手段的诞生。研究团队也正试图找到抑制Vav3蛋白活性的化学物质，以便开发出新疗法以大大延长白血病患者的生存。

doi:10.1182/blood-2010-08-30349
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Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib

Ashu Kumari, Cornelia Brendel, Andreas Hochhaus, Andreas Neubauer, and Andreas Burchert

BCR-ABL overexpression and stem cell quiescence supposedly contribute to the failure of imatinib mesylate (IM) to eradicate chronic myeloid leukemia (CML). However, BCR-ABL expression levels of persisting precursors and the impact of long-term IM therapy on the clearance of CML from primitive and mature bone marrow compartments are unclear. Here, we have shown that the number of BCR-ABL–positive precursors decreases significantly in all bone marrow compartments during major molecular remission (MMR). More importantly, we were able to demonstrate substantially lower BCR-ABL expression levels in persisting MMR colony-forming units (CFUs) compared with CML CFUs from diagnosis. Critically, lower BCR-ABL levels may indeed cause IM insensitivity, because primary murine bone marrow cells engineered to express low amounts of BCR-ABL were substantially less sensitive to IM than BCR-ABL–overexpressing cells. BCR-ABL overexpression in turn catalyzed the de novo development of point mutations to a greater extent than chemical mutagenesis. Thus, MMR is characterized by the persistence of CML clones with low BCR-ABL expression that may explain their insensitivity to IM and their low propensity to develop IM resistance through kinase point mutations. These findings may have implications for future treatment strategies of residual disease in CML.