Role of drug transport and metabolism in the chemoresistance of acute myeloid leukemia
Abstract
Acute myeloid leukemia is a clonal but heterogeneous disease differing in molecular pathogenesis, clinical features and response to chemotherapy. This latter frequently consists of a combination of cytarabine and anthracyclines, although etoposide, demethylating agents, and other drugs are also used. Unfortunately, chemoresistance is a common and serious problem. Multiple mechanisms account for impaired effectiveness of drugs and reduced levels of active agents in target cells. The latter can be due to lower drug uptake, increased export or decreased intracellular proportion of active/inactive agent due to changes in the expression/function of enzymes responsible for the activation of pro-drugs and the inactivation of active agents. Characterization of the "resistome", or profile of expressed genes accounting for multi-drug resistance (MDR) phenotype, would permit to predict the lack of response to chemotherapy and would help in the selection of the best pharmacological regime for each patient and moment, and to develop strategies of chemosensitization.
References
Citations
Optimizing Targeted Inhibitors of P-Glycoprotein Using Computational and Structure-Guided Approaches
Related Concepts
Related Feeds
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.
Blood And Marrow Transplantation
The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.
Antimicrobial Resistance (ASM)
Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.
AML: Role of LSD1 by CRISPR (Keystone)
Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.
Antimicrobial Resistance
Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.