Pimenta Débora Bifano, Varela Vanessa Araujo, Datoguia Tarcila Santos, Caraciolo Victória Bulcão, Lopes Gabriel Herculano, Pereira Welbert Oliveira
Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Front Cell Dev Biol. 2021 Nov 19;9:764698. doi: 10.3389/fcell.2021.764698. eCollection 2021.
Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that mediate important functions on hematopoietic cells and leukemic blasts. There are some evidences of how AML modify the architecture and function of these three BM niches, but it has been still unclear how essential those modifications are to maintain AML development. Basic studies and clinical trials have been suggesting that disturbing specific cells and molecules into the BM niches might be able to impair leukemia competencies. Either through niche-specific molecule inhibition alone or in combination with more traditional drugs, the bone marrow microenvironment is currently considered the potential target for new strategies to treat AML patients. This review describes the cellular and molecular constitution of the BM niches under healthy and AML conditions, presenting this anatomical compartment by a new perspective: as a prospective target for current and next generation therapies.
骨髓(BM)是一种高度复杂的组织,它提供重要的调节信号来协调造血作用。驻留细胞和短暂细胞占据一些特征明确的龛位并与其相互作用,从而产生分子和细胞机制,这些机制会干扰该微环境中的细胞分化、迁移、存活和增殖。急性髓系白血病(AML)是成人中最常见且最严重的血液肿瘤,它在骨髓中发生和发展。成骨龛位、血管龛位和网状龛位提供表面共受体、可溶性因子、细胞因子和趋化因子,这些物质介导对造血细胞和白血病母细胞的重要功能。有一些证据表明AML如何改变这三种骨髓龛位的结构和功能,但目前仍不清楚这些改变对于维持AML发展有多重要。基础研究和临床试验表明,干扰骨髓龛位中的特定细胞和分子可能会损害白血病能力。无论是单独通过抑制龛位特异性分子还是与更传统的药物联合使用,骨髓微环境目前都被认为是治疗AML患者新策略的潜在靶点。本综述描述了健康和AML条件下骨髓龛位的细胞和分子组成,从一个新的视角呈现这个解剖区域:作为当前和下一代疗法的潜在靶点。