Therapy for Acute Leukemias and Related Disorders
The primary focus of our clinical team is patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), and myeloproliferative disorders. Our practice is located in the Center for Hematologic Malignancies in the ambulatory clinic at DFCI, but we also see inpatients at Brigham and Women's Hospital. In addition to seeing patients with refractory leukemia and advanced myelodysplasia, we see others with complex or difficult cases who have been referred from outside New England and from other countries. Our goal is to provide the highest level of clinical care and improve the outcome for all patients.Our research involves identifying novel targets involved in the pathophysiology of acute leukemia and myelodysplastic syndrome. Inhibition of the FLT3 tyrosine kinase, for example, may offer benefits in AML patients - especially those whose blasts have an activating mutation in the enzyme - similar to the success of imatinib in the treatment of patients with chronic myeloid leukemia (CML). After conducting several trials with FLT3 inhibitors as single agents in myeloid malignancies, we are now focusing on combining these drugs with chemotherapeutic agents. Our laboratory continues to explore the mechanism of leukemic transformation via mutated FLT3, especially regarding activation of downstream pathways such as protein kinase A or AKT, which may be involved in key aspects of leukemogenesis such as prevention of apoptosis and promotion of self-renewal. Other areas of clinical research include targeted therapy in T cell ALL, based on inhibition of NOTCH activation, a common survival mechanism in such cells; application of intensive "pediatric-type" strategies in adults with ALL; and many novel drugs in AML in AML and MDS including histone deacetylase inhibitors, NEDD-8 inhibitors, HSP90 inhibitors, MEK inhibitors and others.