The unique features of the tumor microenvironment (TME) govern the biological properties of many cancers, including hematological malignancies. TME factors can trigger an invasion and protect against drug cytotoxicity by inhibiting apoptosis and activating specific signaling pathways (e.g. NF-ΚB). TME remodeling is facilitated due to the high self-renewal ability of the bone marrow. Progressing tumor cells can alter some extracellular matrix (ECM) components which act as a barrier to drug penetration in the TME. The initial progression of the cell cycle is controlled by the MAPK pathway (Raf/MEK/ERK) and Hippo pathway, while the final phase is regulated by the PI3K/Akt /mTOR and WNT pathways. This review summarizes the main signaling pathways involved in drug resistance (DR) and some mechanisms by which DR can occur in the bone marrow. The relationship between autophagy, endoplasmic reticulum stress, and cellular signaling pathways in DR and apoptosis is covered in the TME.

中文翻译：

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骨髓微环境在血液系统恶性肿瘤耐药中的作用。

肿瘤微环境 (TME) 的独特特征决定了许多癌症的生物学特性，包括血液系统恶性肿瘤。TME 因子可以通过抑制细胞凋亡和激活特定的信号通路（例如 NF-κB）来触发侵袭和防止药物细胞毒性。由于骨髓的高自我更新能力，促进了 TME 重塑。进展的肿瘤细胞可以改变一些细胞外基质 (ECM) 成分，这些成分在 TME 中充当药物渗透的屏障。细胞周期的初始进程由 MAPK 通路 (Raf/MEK/ERK) 和 Hippo 通路控制，而最后阶段由 PI3K/Akt /mTOR 和 WNT 通路调节。本综述总结了耐药性 (DR) 中涉及的主要信号通路以及 DR 可在骨髓中发生的一些机制。