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Functional interdependence of hematopoietic stem cells and their niche in oncogene promotion of myeloproliferative neoplasms: The 159th biomedical version of it takes two to tango

机译：造血干细胞的功能相互依赖性及其在骨髓增殖性肿瘤的癌基因促进中的位置：第159个生物医学版本的探戈需要两个

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摘要

The role of stem cells in normal and neoplastic hematopoiesis is well established. However, neither normal nor neoplastic hematopoietic stem cells (HSCs) develop in isolation and accumulating evidence indicates that a critical developmental role is played by the perivascular “niche.” The cellular, humoral, and cell surface contacts that provide the proper environment for HSC survival, proliferation, and differentiation are becoming increasingly better understood. A number of studies have established that endothelial cells (ECs), several types of perivascular stromal cells, and megakaryocytes (MKs) provide several cell surface and secreted molecules required for HSC development. Accumulating evidence also indicates that the normal stem cell niche is altered in patients with hematological neoplasms and that the “neoplastic niche” plays an important role in promoting malignant and suppressing normal blood cell development in such patients. To explore this concept in the myeloproliferative neoplasms (MPNs), we employed a murine model to determine the effects of Jak2V617F, an oncogene found in a majority of such patients, in marrow ECs and MKs and their effect on promoting neoplastic and suppressing normal hematopoiesis. We found that Jak2V617F has profound effects on both cell types, which together are critical for the growth advantage and radioresistance shown by Jak2V617F-bearing HSCs. Such findings should provide new approaches to the treatment of patients with MPNs.
机译：干细胞在正常和肿瘤性造血中的作用已得到充分证实。但是，正常的和肿瘤性的造血干细胞（HSC）都不是孤立产生的，越来越多的证据表明，血管周围的“利基”发挥了关键的发展作用。为HSC存活，增殖和分化提供适当环境的细胞，体液和细胞表面接触越来越被理解。大量研究已经证实，内皮细胞（EC），几种类型的血管周围基质细胞和巨核细胞（MK）提供了HSC发育所需的几种细胞表面和分泌分子。越来越多的证据还表明，血液肿瘤患者的正常干细胞生态位发生了变化，“肿瘤生态位”在促进此类患者的恶性肿瘤和抑制正常血细胞发育中起着重要作用。为了在骨髓增生性肿瘤（MPN）中探索这一概念，我们采用了小鼠模型来确定Jak2V617F（在大多数此类患者中发现的癌基因）在骨髓EC和MK中的作用及其在促进肿瘤形成和抑制正常造血中的作用。我们发现，Jak2V617F对两种细胞类型都有深远的影响，这对于带有Jak2V617F的HSC所显示的生长优势和抗辐射性至关重要。这些发现应提供治疗MPNs的新方法。

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    Huichun Zhan; Kenneth Kaushansky;

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  • 年(卷),期 -1(70),-1
  • 年度 -1
  • 页码 24–30
  • 总页数 11
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