Chapters authored
Survivin: Identification of Selective Functional Signaling Pathways inTransformed Cells and Identification of a New Splice Variant with Growth Survival Activity
Part of the book: Advances in Cancer Therapy
Trafficking of Acute Leukemia Cells – Chemokine Receptor Pathways that Modulate Leukemia Cell Dissemination
Part of the book: Acute Leukemia
Molecular Interaction Between the Microenvironment and FLT3/ITD+ AML Cells Leading to the Refractory Phenotype
Internal tandem duplication mutations in the FLT3 gene (FLT3/ITD) are detected in 10–15% of children and 30% of adult patients with AML and are associated with an extremely poor prognosis. Although several antagonists against FLT3/ITD have been developed, few of them are effective for the treatment of FLT3/ITD+ AML because of the emergence of drug-resistant cells. The mechanisms responsible for drug resistance include the acquisition of additional mutations in the FLT3 gene and/or activation of other prosurvival pathways such as microenvironment-mediated resistance. Recent studies have strongly suggested that the reciprocal interaction between the microenvironment and AML cells generates specific machinery that leads to chemoresistance. This chapter describes the molecular mechanism responsible for the refractory phenotype of FLT3/ITD+ AML cells resulting from the communication between the microenvironment and FLT3/ITD+ leukemia cells. Understanding this mechanism enables the discovery of novel and innovative therapeutic interventions for resistant FLT3/ITD+ AML.
Part of the book: Myeloid Leukemia