间充质基质细胞(MSCs)是骨髓(BM)生态位的结构成分,它们在功能上与造血干细胞和更多分化的祖细胞相互作用,有助于造血调节。如今,越来越多的证据表明MSC对恶性造血的进一步重要贡献。在B细胞急性淋巴细胞白血病(B-ALL)的背景下,MSCs可以在白血病支持微环境的定义中发挥关键作用,影响疾病的发病机制在不同的步骤,包括发病,维护和进展。B-ALL细胞劫持BM微环境,包括居住在BM生态位的MSC,反过来保护白血病细胞,并通过不同的机制保护它们免受化疗剂的侵害。现在有证据表明,改变的MSCs可以通过提供营养而成为白血病细胞的宝贵盟友,细胞因子,支持生存的信号和交换细胞器,如下文所述。对MSCs培育和保护B-ALL母细胞的机制的研究可能有助于寻找靶向白血病BM微环境的新药物候选物。其中一些微环境靶向策略已经在临床前或临床试验中,如果结合白血病定向治疗,可能是改善复发/难治性患者预后的有价值的选择,其管理代表了未满足的医疗需求。
Mesenchymal stromal cells (MSCs) are structural components of the bone marrow (BM) niche, where they functionally interact with hematopoietic stem cells and more differentiated progenitors, contributing to hematopoiesis regulation. A growing body of evidence is nowadays pointing to a further crucial contribution of MSCs to malignant hematopoiesis. In the context of B-cell acute lymphoblastic leukemia (B-ALL), MSCs can play a pivotal role in the definition of a leukemia-supportive microenvironment, impacting on disease pathogenesis at different steps including onset, maintenance and progression. B-ALL cells hijack the BM microenvironment, including MSCs residing in the BM niche, which in turn shelter leukemic cells and protect them from chemotherapeutic agents through different mechanisms. Evidence is now arising that altered MSCs can become precious allies to leukemic cells by providing nutrients, cytokines, pro-survivals signals and exchanging organelles, as hereafter reviewed. The study of the mechanisms exploited by MSCs to nurture and protect B-ALL blasts can be instrumental in finding new druggable candidates to target the leukemic BM microenvironment. Some of these microenvironment-targeting strategies are already in preclinical or clinical experimentation, and if coupled with leukemia-directed therapies, could represent a valuable option to improve the prognosis of relapsed/refractory patients, whose management represents an unmet medical need.