日本研究人员最新发现,引起急性骨髓性白血病复发的罪魁——白血病干细胞会“躲”在骨髓与骨的交界处“装死”,以躲过抗癌药物的攻击。研究人员利用细胞因子将其激活,从而提高抗癌药物的疗效。
日本理化研究所的研究人员以实验鼠为研究对象进行了相关实验。他们发现白血病干细胞会聚集在骨髓与骨的交界处,并且其细胞分裂周期处于静止状态。因为抗癌药物多是以分裂周期快的细胞为标靶开发的,所以停止细胞分裂的白血病干细胞就表现出耐药性。
在这一发现的基础上,研究人员尝试用生理活性物质激活白血病干细胞的分裂周期,然后再施以抗癌药物治疗。他们先将白血病干细胞移植到实验鼠体内,使其表现出白血病症状,然后将生理活性物质之一的细胞因子注射到实验鼠体内。
结果表明,与没有接受细胞因子注射的实验鼠相比,同样剂量的化疗药物杀灭白血病干细胞的数量提高了3至5倍。
该成果刊登在新一期《自然·生物技术》杂志上。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Biotechnology 14 February 2010 | doi:10.1038/nbt.1607
Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML
Yoriko Saito1, Naoyuki Uchida2, Satoshi Tanaka3, Nahoko Suzuki1, Mariko Tomizawa-Murasawa1, Akiko Sone1, Yuho Najima1, Shinsuke Takagi1,2, Yuki Aoki1, Atsushi Wake2, Shuichi Taniguchi2, Leonard D Shultz4 & Fumihiko Ishikawa1
Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML)1, 2, 3. We have previously reported4 that CD34+CD38? human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rγnull mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells in vivo. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.