Molecular mechanisms of resistance to STI571 in chronic... : Current Opinion in Hematology (original) (raw)

Hematologic malignancies

Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, California, USA.

Correspondence to Charles L. Sawyers, MD, UCLA School of Medicine, Division of Hematology and Oncology, 11–934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095–1678, USA; e-mail: [email protected]

Supported by grants from the Leukemia and Lymphoma Society, the National Cancer Institute (C.L.S.) and a USPHS National Research Service Award GM07185 (M.E.G.)

Abstract

Therapeutic use of the recently FDA-approved drug STI571 has been successful in the treatment of Philadelphia chromosome–positive leukemias. STI571 is a small molecule inhibitor with activity against BCR-ABL, the deregulated tyrosine kinase responsible for initiation and maintenance of the disease in the chronic phase of chronic myeloid leukemia (CML). Clinical trials demonstrated the ability of STI571 to induce remissions in patients with chronic phase CML with only rare relapses after 18 months of follow-up. However, in patients with more advanced stages of disease, responses to STI571 were less common and often transient. Studies investigating the molecular mechanisms of resistance to this novel compound have progressed rapidly and point to the continued importance of BCR-ABL in disease maintenance even at its latest stages. Here the authors review recent work aimed at elucidating the nature of STI51 resistance.