澳大利亚莫纳什大学Ross A. Dickins团队研制了急性髓系白血病致瘤状态与分化状态的相互转化。 该研究于2019年8月发表于国际一流学术期刊《细胞—干细胞》上。

研究团队在AML小鼠和人类模型中发现，当派系决定转录因子PU.1的内源性表达被干扰或已建立的分化治疗被撤销后，一些成熟的白血病细胞可以去分化并重新获得克隆和白血病特性。他们的研究结果揭示了AML中CSC成熟的可塑性，强调了在一系列分化状态下治疗性根除癌细胞的必要性。

据了解，肿瘤是由表型异质性癌细胞组成的，这些细胞往往类似于其起源谱系的各种分化状态。在这一体系中，人们认为肿瘤干细胞（CSCs）的一个未成熟亚群分化为非致瘤的后代，为明确根除CSCs或诱导其分化的治疗策略提供了理论依据。这些方法在临床上的成功依赖于CSC分化是单向不可逆的，然而即使在典型的分级恶性肿瘤中，如急性髓系白血病（AML），这个问题仍然没有得到解决。


附：英文原文

Title: Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia

Author: Mark D. McKenzie, Margherita Ghisi, Ethan P. Oxley, Matthew E. Ritchie, Johannes Zuber, Ross A. Dickins

Issue&Volume: Volume 25 Issue 2

Abstract: Tumors are composed of phenotypically heterogeneous cancer cells that often resemble various differentiation states of their lineage of origin. Within this hierarchy, it is thought that an immature subpopulation of tumor-propagating cancer stem cells (CSCs) differentiates into non-tumorigenic progeny, providing a rationale for therapeutic strategies that specifically eradicate CSCs or induce their differentiation. The clinical success of these approaches depends on CSC differentiation being unidirectional rather than reversible, yet this question remains unresolved even in prototypically hierarchical malignancies, such as acute myeloid leukemia (AML). Here, we show in murine and human models of AML that, upon perturbation of endogenous expression of the lineage-determining transcription factor PU.1 or withdrawal of established differentiation therapies, some mature leukemia cells can de-differentiate and reacquire clonogenic and leukemogenic properties. Our results reveal plasticity of CSC maturation in AML, highlighting the need to therapeutically eradicate cancer cells across a range of differentiation states.

DOI: https://doi.org/10.1016/j.stem.2019.07.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30299-1