As is clear to anyone who pays medical insurance premiums or has undergone any kind of medical procedure, the business of health care is an expensive one. The technology is expensive. The research is expensive. The services are expensive. Meanwhile, health care consumers complain of poor service and inadequate care. In short, health care in the United States appears to be broken.
Enter Harvard Business School’s Life Sciences & Health Care Initiative, which brings together faculty from diverse parts of HBS to both conduct research on the sector and prepare future leaders in health care and life sciences. The initiative was started in 1997 at the behest of Dean Kim Clark. We asked professor Gary P. Pisano, who heads up the initiative, to give HBS Working Knowledge a peek into the work being accomplished in the initiative.
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Effects of MLN518, A Dual FLT3 and KIT Inhibitor, on Normal and Malignant Hematopoiesis.
, Shen LJ
, LaRosee P
, Demehri S
, Heinrich MC
, Braziel RM
, McGreevey L
, Haley AD
, Giese N
, Druker BJ
, Deininger MW
Internal tandem duplications (ITD) of the FLT3 receptor tyrosine kinase are found in approximately 30% of patients with acute myelogenous leukemia (AML) and are associated with a poor prognosis. FLT3 ITD mutations result in constitutive kinase activation and are thought to be pathogenetically relevant, implicating FLT3 as a plausible therapeutic target. MLN518 (formerly CT53518) is a small molecule inhibitor of the FLT3, KIT and PDGFR tyrosine kinases with significant activity in murine models of FLT3 ITD-positive leukemia. Given the importance of FLT3 and KIT for normal hematopoietic progenitor cells, we analyzed the effect of MLN518 on murine hematopoiesis under steady state conditions, after chemotherapy-induced myelosuppression and during bone marrow transplantation. In these assays, we show that MLN518 has mild toxicity toward normal hematopoiesis at concentrations that are effective in treating FLT3 ITD-positive leukemia in mice. We also demonstrate that MLN518 preferentially inhibits the growth of blast colonies from FLT3 ITD-positive compared to ITD-negative AML patients, at concentrations that do not significantly affect colony formation by normal human progenitor cells. In analogy to imatinib in BCR-ABL-positive acute leukemia, MLN518-induced remissions may not be durable. Our studies provide the basis for integrating this compound into chemotherapy and transplantation protocols.