近日,，辛辛那提大學（UC）Hoxworth血液中心研究人員發(fā)現(xiàn)治療白血病的新靶基因。這一研究結果將于7月26日刊登在美國血液學會Blood雜志上,。
這項研究由在加州大學醫(yī)學部兒科副教授和Hoxworth血液中心研究部主任Jose Cancelas博士領導,，研究團隊在動物模型中抑制Vav3蛋白，從而控制細胞信號轉導,，動物發(fā)展患有 BCR-ABL淋巴白血病被延遲,。
盡管治療白血病的治療手段一直在進步，但BCR-ABL淋巴白血病患者的治療結果卻是非常差的,，因為這一類型的白血病易產(chǎn)生耐藥性,。總之研究發(fā)現(xiàn)Vav3蛋白遺傳缺陷能控制白血病BCR-ABL的發(fā)病,。
Cancelas表示：這一發(fā)現(xiàn)可能導致新的多靶治療白血病手段的誕生,。研究團隊也正試圖找到抑制Vav3蛋白活性的化學物質，以便開發(fā)出新療法以大大延長白血病患者的生存,。（生物谷：Bioon.com）
doi:10.1182/blood-2010-08-30349
PMC:
PMID:
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.
