美國科學家近日發(fā)現(xiàn)一種控制干細胞快速產(chǎn)生和分化的基因,，這一發(fā)現(xiàn)有望導致對于白血病和其它血癌的新型療法。相關論文4月7日發(fā)表在《癌細胞》（Cancer Cell）上,。
這一基因名為JunB，它位于調(diào)控造血干細胞（HSCs）增殖和分化的分子與環(huán)境信號復雜網(wǎng)絡的中央,。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,，會出現(xiàn)骨髓系的擴充,，形成一種成熟白細胞對抗感染。移植后6到12個月,，這種擴充會導致骨髓增生性疾病,，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會導致白血病,。
就如紅綠燈限速并導引車輛一樣，JunB縮減HSCs的增殖及分化速度,。缺失JunB,，HSCs就失去了對來自蛋白受體Notch和TGF-beta的信號作出反應的能力，這兩種蛋白受體位于細胞表面,，對決定細胞命運具有關鍵性作用,。
論文通訊作者、美國加州大學舊金山分校醫(yī)學系的Emmanuelle Passegué說：“通過揭示這一機制,，某一天我們也許能夠在基因調(diào)控網(wǎng)絡中確定正常HSCs與白血病干細胞的區(qū)別,。這將使我們能夠開發(fā)更多的標靶療法。雖然目前這些治療性應用尚未產(chǎn)生，但它們在血液/白血病領域能很快實現(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.
