Progress Against Blood Diseases—In two recent papers in the journal Blood—the weekly journal published by the American Society of Hematology—Einstein researchers describe novel targets for attacking two important blood diseases mainly affecting the elderly: myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). MDS comprises incurable blood disorders in which the bone marrow produces low numbers of red cells, white cells and platelets. About 15,000 patients are diagnosed each year with MDS. One-third of MDS patients go on to develop AML, a blood-and-bone marrow cancer that has a five-year survival rate of only 25 percent. MDS and AML both originate from disease-causing stem cells, which don’t divide often and therefore resist chemotherapy, thereby damaging DNA of rapidly dividing cells. Effective treatments or cures for MDS and AML therefore require targeting the stem-cell aberrations that cause them. In the first study, Dr. Amit Verma and colleagues analyzed stem cells from MDS and AML patients and found that interleukin 8 (IL8) was consistently overexpressed in those cells, as was IL8’s receptor, CXCR2. They demonstrated that CXCR2 is a potential therapeutic target for treating both MDS and AML. The second study, led by Dr. Ulrich Steidl’s team found that inhibiting another promising MDS/AML target—the kinase PAK1—slowed the growth of four human AML cell lines via cell death, and that MDS patients with high PAK1 expression in bone marrow CD34+ cells have significantly worse survival compared patients with PAK1low-expression. Their findings support using PAK1 inhibitors as a therapeutic strategy for MDS and AML Dr. Verma is professor of medicine and of developmental and molecular biology. Dr Steidl is associate professor of cell biology and of medicine, and is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research.
Posted on: Friday, July 17, 2015