混合性白血病(mixed lineage leukaemia, MLL)是一種具有侵襲性的急性骨髓性白血病(acute myeloid leukaemia)。
來自英國曼徹斯特大學帕特森癌癥研究所(Paterson Institute for Cancer Research)的一個研究小組鑒定出混合性白血病(MLL)的一種新的藥物靶標,，即酶LSD1,。LSD1有助于控制某些致癌基因是被關閉還是被開啟，而且是維持白血病干細胞潛能的一種關鍵性的調節(jié)物,。阻斷這種酶就可阻止促進癌癥產生的蛋白表達,。
來自英國癌癥研究協(xié)會帕特森藥物開發(fā)中心(Cancer Research UK’s Paterson Drug Discovery Unit)的科學家們合成出阻斷LSD1的分子。論文通信作者和英國癌癥研究協(xié)會白血病生物學實驗室小組負責人Tim Somervaille博士證實這些分子能夠阻止從患有混合性白血病(MLL)病人身上提取的白血病細胞生長,，同時也阻止來自患有MLL疾病的小鼠的白血病細胞生長,。
急性骨髓性白血病病人存活率一直比較低?；加谢旌闲园籽〉牟∪撕茈y用當前的治療方法,，如密集化療(intensive chemotherapy)和骨髓移植，獲得治愈,，而且他們目前還不能獲得針對性藥物來治療,，因而他們迫切需要新的藥物。
在當前研究中,，盡管研究人員還需開展更多研究來進一步測試這些分子,，但是這些發(fā)現(xiàn)已經(jīng)為人們在未來開發(fā)出新的治療方法打下堅實的基礎。(生物谷：towersimper編譯)
doi:10.1016/j.ccr.2012.03.014
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The Histone Demethylase KDM1A Sustains the Oncogenic Potential of MLL-AF9 Leukemia Stem Cells
William J. Harris1, Xu Huang1, James T. Lynch1, Gary J. Spencer1, James R. Hitchin2, Yaoyong Li3, Filippo Ciceri1, Julian G. Blaser1, Brigit F. Greystoke1, Allan M. Jordan2, Crispin J. Miller3, Donald J. Ogilvie2, Tim C.P. Somervaille
Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogs active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia, which may be selectively targeted to therapeutic effect.
