Multidrug resistance in hematological malignancy.
The recent treatment of hematological malignancies appears to be unsatisfactory in child and adult patients with acute myeloid leukemia and adult patients with acute lymphocytic leukemia. A major problem in the treatment of leukemia is caused by the development of drug resistance to chemotherapeutic agents, which is already present at diagnosis or after chemotherapy as a minimal residual disease, their resistance having originated from genetic or epigenetic mutations during prior growth of the leukemia clone. It was suggested that the mechanisms of drug resistance consist of drug resistance proteins, which work as a drug efflux pump. These are the permeability-related glycoprotein (P-Gp), the multidrug-resistance associated protein (MRP), the lung resistance protein (LRP), and other MDR proteins such as the transporter associated with antigen processing (TAP), anthracyclin resistance associated protein (ARA), MRP 2-7, and breast cancer resistance protein (BCRP). In addition, anti-apoptosis mechanisms, alterations of tumor suppressor genes, altered immunogenicity, drug resistance mechanisms for individual drugs, and clinical risk factors such as white blood cell count, age, and other factors have been reported to act in drug resistance singly or in combinations. Here we describe the update of research on the biology of MDR in the hematological malignancies and also discuss how to overcome MDR and adapt the updated treatment methods in the clinical medical field.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D017209:Apoptosis; D002648:Child; D018432:Drug Resistance, Multiple / Q000235:genetics; D019450:Genes, MDR; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation; D009363:Neoplasm Proteins; D010641:Phenotype; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C000715087:ABCC2 protein, human