School of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Int J Mol Sci. 2022 Feb 18;23(4):2293. doi: 10.3390/ijms23042293.
Self-maintaining hematopoietic stem cells are a cell population that is primarily 'at risk' to malignant transformation, and the cell-of-origin for some leukemias. Tissue-specific stem cells replenish the different types of functional cells within a particular tissue to meet the demands of an organism. For hematopoietic stem cells, this flexibility is important to satisfy the changing requirements for a certain type of immune cell, when needed. From studies of the natural history of childhood acute lymphoblastic leukemia, an initial oncogenic and prenatal insult gives rise to a preleukemic clone. At least a second genomic insult is needed that gives rise to a leukemia stem cell: this cell generates a hierarchy of leukemia cells. For some leukemias, there is evidence to support the concept that one of the genomic insults leads to dysregulation of the tissue homeostatic role of hematopoietic stem cells so that the hierarchy of differentiating leukemia cells belongs to just one cell lineage. Restricting the expression of particular oncogenes in transgenic mice to hematopoietic stem and progenitor cells led to different human-like lineage-restricted leukemias. Lineage restriction is seen for human leukemias by virtue of their sub-grouping with regard to a phenotypic relationship to just one cell lineage.
自我维持的造血干细胞是一个主要处于“危险”状态的细胞群体，容易发生恶性转化，也是某些白血病的起源细胞。组织特异性干细胞补充特定组织内不同类型的功能细胞，以满足生物体的需求。对于造血干细胞来说，这种灵活性对于满足对特定类型免疫细胞的不断变化的需求非常重要。从儿童急性淋巴细胞白血病的自然病史研究中可以看出，最初的致癌和产前损伤会导致前白血病克隆。至少需要第二次基因组损伤才能产生白血病干细胞：这种细胞产生白血病细胞的层次结构。对于某些白血病，有证据支持这样一种概念，即其中一个基因组损伤会导致造血干细胞的组织稳态作用失调，从而使分化的白血病细胞的层次结构仅属于一个细胞谱系。将特定的癌基因在转基因小鼠中的表达限制在造血干细胞和祖细胞上，导致了不同的类似于人类的谱系受限的白血病。通过与仅一个细胞谱系的表型关系，人类白血病的亚群分组就可以看到谱系限制。
