美國(guó)科學(xué)家近日發(fā)現(xiàn)一種控制干細(xì)胞快速產(chǎn)生和分化的基因,，這一發(fā)現(xiàn)有望導(dǎo)致對(duì)于白血病和其它血癌的新型療法,。相關(guān)論文4月7日發(fā)表在《癌細(xì)胞》（Cancer Cell）上,。
這一基因名為JunB,，它位于調(diào)控造血干細(xì)胞（HSCs）增殖和分化的分子與環(huán)境信號(hào)復(fù)雜網(wǎng)絡(luò)的中央,。研究人員分別在培養(yǎng)皿和小鼠體內(nèi)研究了缺乏JunB的HSCs的行為,，結(jié)果發(fā)現(xiàn),，小鼠體內(nèi)移植入HSCs后,，會(huì)出現(xiàn)骨髓系的擴(kuò)充，形成一種成熟白細(xì)胞對(duì)抗感染,。移植后6到12個(gè)月,，這種擴(kuò)充會(huì)導(dǎo)致骨髓增生性疾病，有可能發(fā)展成白血病,。這一發(fā)現(xiàn)表明,，增生的缺乏JunB的HSCs會(huì)導(dǎo)致白血病。
就如紅綠燈限速并導(dǎo)引車輛一樣,，JunB縮減HSCs的增殖及分化速度,。缺失JunB，HSCs就失去了對(duì)來(lái)自蛋白受體Notch和TGF-beta的信號(hào)作出反應(yīng)的能力，這兩種蛋白受體位于細(xì)胞表面,，對(duì)決定細(xì)胞命運(yùn)具有關(guān)鍵性作用,。
論文通訊作者、美國(guó)加州大學(xué)舊金山分校醫(yī)學(xué)系的Emmanuelle Passegué說(shuō)：“通過(guò)揭示這一機(jī)制,，某一天我們也許能夠在基因調(diào)控網(wǎng)絡(luò)中確定正常HSCs與白血病干細(xì)胞的區(qū)別,。這將使我們能夠開(kāi)發(fā)更多的標(biāo)靶療法。雖然目前這些治療性應(yīng)用尚未產(chǎn)生,，但它們?cè)谘?白血病領(lǐng)域能很快實(shí)現(xiàn),。”（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Cell，doi:10.1016/j.ccr.2009.02.016,，Marianne Santaguida,，Emmanuelle Passegué
JunB Protects against Myeloid Malignancies by Limiting Hematopoietic Stem Cell Proliferation and Differentiation without Affecting Self-Renewal
Marianne Santaguida1,Koen Schepers1,Bryan King1,Amit J. Sabnis2,E. Camilla Forsberg3,Joanne L. Attema4,Benjamin S. Braun2andEmmanuelle Passegué1,,
1 The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
2 Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA
3 Institute for Biology of Stem Cells, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
4 Institute for Experimental Medical Science, Lund University, 221 84 Lund, Sweden
Summary
Loss of the JunB/AP-1 transcription factor induces a myeloproliferative disease (MPD) arising from the hematopoietic stem cell (HSC) compartment. Here, we show that junB inactivation deregulates the cell-cycle machinery and increases the proliferation of long-term repopulating HSCs (LT-HSCs) without impairing their self-renewal or regenerative potential invivo. We found that JunB loss destabilizes a complex network of genes and pathways that normally limit myeloid differentiation, leading to impaired responsiveness to both Notch and TGF- signaling due in part to transcriptional deregulation of the Hes1 gene. These results demonstrate that LT-HSC proliferation and differentiation are uncoupled from self-renewal and establish some of the mechanisms by which JunB normally limits the production of myeloid progenitors, hence preventing initiation of myeloid malignancies.
