Targeting the Microenvironment in MDS: The Final Frontier

Myelodysplastic syndromes Myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS) are a heterogeneous group of malignant disorders of hematopoietic stem and progenitor cells (HSPC), mainly characterized by ineffective hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. leading to peripheral cytopenias and progressive bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… . 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 bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the 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 engraftment: Refers to how well a graft (donor cells) is accepted by the host (the patient) after a bone marrow or stem cell transplant. Several factors contribute to better engraftment - physical condition of the patient, how severe the disease is, type of donor available, age of patient. Successful… of normal, allogeneic HSPCs in patients with MDS undergoing bone marrow transplant bone marrow transplant: A bone marrow transplant (BMT) is also called a stem cell transplant (SCT) or hematopoietic stem cell transplant (HSCT).The procedure replaces unhealthy blood-forming stem cells with healthy ones and offers some patients the possibility of a cure. But for many patients, a BMT is not an option due… . 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.