Teodorescu Patric, Pasca Sergiu, Dima Delia, Tomuleasa Ciprian, Ghiaur Gabriel
Department of Hematology, Iuliu Hategan University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Oncology, The Johns Hopkins Hospital, Johns Hopkins Medicine, Baltimore, MD, United States.
Front Pharmacol. 2020 Jul 9;11:1044. doi: 10.3389/fphar.2020.01044. eCollection 2020.
Myelodysplastic syndromes (MDS) are a heterogeneous group of malignant disorders of hematopoietic stem and progenitor cells (HSPC), mainly characterized by ineffective hematopoiesis leading to peripheral cytopenias and progressive bone marrow failure. While clonal dominance is nearly universal at diagnosis, most genetic mutations identified in patients with MDS do not provide a conspicuous advantage to the malignant cells. In this context, malignant cells alter their adjacent bone marrow microenvironment (BME) and rely on cell extrinsic factors to maintain clonal dominance. The profoundly disturbed BME favors the myelodysplastic cells and, most importantly is detrimental to normal hematopoietic cells. Thus, the MDS microenvironment not only contributes to the observed cytopenias seen in these patients but could also negatively impact the engraftment of normal, allogeneic HSPCs in patients with MDS undergoing bone marrow transplant. Therefore, successful therapies in MDS should not only target the malignant cells but also reprogram their bone marrow microenvironment. Here, we will provide a synopsis of how drugs currently used or on the verge of being approved for the treatment of MDS may achieve this goal.
骨髓增生异常综合征（MDS）是造血干细胞和祖细胞（HSPC）的一组异质性恶性疾病，主要特征是无效造血导致外周血细胞减少和进行性骨髓衰竭。虽然在诊断时克隆优势几乎普遍存在，但在MDS患者中鉴定出的大多数基因突变并未给恶性细胞带来明显优势。在这种情况下，恶性细胞改变其相邻的骨髓微环境（BME），并依赖细胞外因子来维持克隆优势。严重紊乱的BME有利于骨髓增生异常细胞，最重要的是对正常造血细胞有害。因此，MDS微环境不仅导致这些患者出现血细胞减少，还可能对接受骨髓移植的MDS患者中正常异体HSPC的植入产生负面影响。因此，MDS的成功治疗不仅应针对恶性细胞，还应重新编程其骨髓微环境。在此，我们将概述目前用于治疗MDS或即将获批用于治疗MDS的药物如何实现这一目标。
