A 50-year-old woman has had easy fatigability and noted a dragging sensation in her abdomen for the past 5 months. Physical examination reveals that she is afebrile. She has marked splenomegaly, but no lymphadenopathy. Laboratory studies show her total WBC count is 250,000/mm3 with WBC differential count showing 64% segmented neutrophils, 11% band neutrophils, 7% metamyelocytes, 5% myelocytes, 4% myeloblasts, 3% lymphocytes, 2% basophils, 2% eosinophils, and 2% monocytes. A bone marrow biopsy is performed, and karyotypic analysis of the cells reveals a t (9;22) translocation. Medical treatment with a drug having which of the following modes of action is most likely to produce a complete remission in this patient?
This patient has a classic history and t (9;22) translocation with chronic myelogenous leukemia. The translocation causes uncontrolled nonreceptor tyrosine kinase activity of the BCR-ABL fusion gene. These patients undergo remission with drugs such as imatinib that inhibit tyrosine kinases. Agents that activate caspases theoretically may help in many cases, especially when apoptosis is blocked as in tumors with BCL2 overexpression. Antibodies to epithelial growth factor receptors, such as ERBB2 (HER2) receptors, are beneficial in certain breast tumors with amplification of this gene. Delivery of p53 into cells by viral vectors has not yet been proven to be valuable in cancer treatment, and it is not used in chronic myelogenous leukemia. Translocation of b-catenin to the nucleus occurs in colon cancers when there is a mutational loss of APC genes.
Activating cellular caspases
Antibody binding to EGF receptors
Delivering normal p53 into cells with viral vectors
Inhibiting tyrosine kinase activity
Neoplasia