日本研究人員最新發(fā)現(xiàn),,引起急性骨髓性白血病復(fù)發(fā)的罪魁——白血病干細(xì)胞會(huì)“躲”在骨髓與骨的交界處“裝死”,,以躲過(guò)抗癌藥物的攻擊。研究人員利用細(xì)胞因子將其激活,,從而提高抗癌藥物的療效,。
日本理化研究所的研究人員以實(shí)驗(yàn)鼠為研究對(duì)象進(jìn)行了相關(guān)實(shí)驗(yàn)。他們發(fā)現(xiàn)白血病干細(xì)胞會(huì)聚集在骨髓與骨的交界處,,并且其細(xì)胞分裂周期處于靜止?fàn)顟B(tài),。因?yàn)榭拱┧幬锒嗍且苑至阎芷诳斓募?xì)胞為標(biāo)靶開發(fā)的,,所以停止細(xì)胞分裂的白血病干細(xì)胞就表現(xiàn)出耐藥性。
在這一發(fā)現(xiàn)的基礎(chǔ)上,,研究人員嘗試用生理活性物質(zhì)激活白血病干細(xì)胞的分裂周期,,然后再施以抗癌藥物治療。他們先將白血病干細(xì)胞移植到實(shí)驗(yàn)鼠體內(nèi),,使其表現(xiàn)出白血病癥狀,,然后將生理活性物質(zhì)之一的細(xì)胞因子注射到實(shí)驗(yàn)鼠體內(nèi)。
結(jié)果表明,,與沒(méi)有接受細(xì)胞因子注射的實(shí)驗(yàn)鼠相比,,同樣劑量的化療藥物殺滅白血病干細(xì)胞的數(shù)量提高了3至5倍。
該成果刊登在新一期《自然·生物技術(shù)》雜志上,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.