Losing Sense of Self and Surroundings: Hematopoietic Stem Cell Aging and Leukemic Transformation.
Losing Sense of Self and Surroundings: Hematopoietic Stem Cell Aging and Leukemic Transformation.
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DOI：
10.1016/j.molmed.2019.04.006
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发表时间：
2019-06
影响因子：
13.6
通讯作者：
Passegué E
中科院分区：
文献类型：
--
作者：
Verovskaya EV;Dellorusso PV;Passegué E
衰老导致造血系统功能下降，表现为老年人血液病发病率增加。造血完整性随年龄的恶化部分源于造血干细胞（HSC）功能的退化。在这里，我们回顾了最近的研究结果，确定代谢程序的变化和表观遗传特性的丧失作为老年HSC功能障碍的主要驱动因素，以及它们在年龄相关性克隆造血（CML）背景下促进白血病发作的作用。我们讨论了来自老年骨髓（BM）微环境的炎症和生长信号如何促进细胞内在HSC衰老表型并有利于白血病的发展。最后，我们讨论了如何代谢，表观遗传和炎症途径可以有针对性地提高旧HSC的健身和防止白血病转化。
Aging leads to functional decline of the hematopoietic system, manifested by an increased incidence of hematological disease in the elderly. Deterioration of hematopoietic integrity with age originates in part from the degraded functionality of hematopoietic stem cells (HSCs). Here, we review recent findings identifying changes in metabolic programs and loss of epigenetic identity as major drivers of old HSC dysfunction and their role in promoting leukemia onset in the context of age-related clonal hematopoiesis (ARCH). We discuss how inflammatory and growth signals from the aged bone marrow (BM) microenvironment contribute to cell-intrinsic HSC aging phenotypes and favor leukemia development. Finally, we address how metabolic, epigenetic, and inflammatory pathways could be targeted to enhance old HSC fitness and prevent leukemic transformation.
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影响因子：
30.8
作者：
Busque L;Patel JP;Figueroa ME;Vasanthakumar A;Provost S;Hamilou Z;Mollica L;Li J;Viale A;Heguy A;Hassimi M;Socci N;Bhatt PK;Gonen M;Mason CE;Melnick A;Godley LA;Brennan CW;Abdel-Wahab O;Levine RL
通讯作者：
Levine RL
影响因子：
8.8
作者：
Brown K;Xie S;Qiu X;Mohrin M;Shin J;Liu Y;Zhang D;Scadden DT;Chen D
通讯作者：
Chen D
影响因子：
64.5
作者：
Bernitz, Jeffrey M.;Kim, Huen Suk;MacArthur, Ben;Sieburg, Hans;Moore, Kateri
通讯作者：
Moore, Kateri
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI
影响因子：
82.9
作者：
Chen, Jiahao;Kao, Yun-Ruei;Steidl, Ulrich
通讯作者：
Steidl, Ulrich