Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space.
Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space.
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DOI：
10.1038/s41467-017-02376-5
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发表时间：
2018-02-06
影响因子：
16.6
通讯作者：
Lo Celso C
中科院分区：
文献类型：
--
作者：
Akinduro O;Weber TS;Ang H;Haltalli MLR;Ruivo N;Duarte D;Rashidi NM;Hawkins ED;Duffy KR;Lo Celso C
白血病逐渐侵袭骨髓(BM)，通过尚未完全了解的机制超越健康的造血。结合细胞数量测量和短时间尺度双脉冲标记法，我们同时测定了原始造血室和急性髓系白血病(AML)的增殖动力学。我们观察到，在整个疾病进展过程中，每小时进入S期的急性髓细胞白血病细胞比例不变，在高渗透水平时有大量的骨髓细胞流出。对于健康的造血，我们发现造血干细胞(HSCs)对细胞生产做出了重大贡献，但我们在表型上识别了具有增强植入能力的静止亚群。在急性髓系白血病进展过程中，我们观察到，尽管总体种群数量急剧减少，但多能祖细胞每小时进入S期的比例保持不变。原始种群从BM中丢失，其动力学与驱逐一致，与细胞周期状态无关，但静止的HSC亚群除外，它更耐消除。白血病细胞是如何通过与造血细胞竞争而侵入骨髓的，目前尚不清楚。在这里，作者使用详细的细胞数量测量结合双脉冲标记方法来确定增殖率，并跟踪AML疾病进展的体内动力学。
Leukaemia progressively invades bone marrow (BM), outcompeting healthy haematopoiesis by mechanisms that are not fully understood. Combining cell number measurements with a short-timescale dual pulse labelling method, we simultaneously determine the proliferation dynamics of primitive haematopoietic compartments and acute myeloid leukaemia (AML). We observe an unchanging proportion of AML cells entering S phase per hour throughout disease progression, with substantial BM egress at high levels of infiltration. For healthy haematopoiesis, we find haematopoietic stem cells (HSCs) make a significant contribution to cell production, but we phenotypically identify a quiescent subpopulation with enhanced engraftment ability. During AML progression, we observe that multipotent progenitors maintain a constant proportion entering S phase per hour, despite a dramatic decrease in the overall population size. Primitive populations are lost from BM with kinetics that are consistent with ousting irrespective of cell cycle state, with the exception of the quiescent HSC subpopulation, which is more resistant to elimination. How leukaemia cells invade the bone marrow by outcompeting haematopoietic cells is still unclear. Here, the authors used detailed cell number measurements in conjunction with a dual pulse labelling method to determine proliferation rates and followed the in vivo dynamics of AML disease progression.
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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
影响因子：
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作者：
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Rodewald, Hans-Reimer