Abstract
Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder that presents a poor survival for patients treated with standard therapies other than stem-cell transplantation. Multi-drug resistance (MDR) to simultaneous drugs used in chemotherapy is a major concern in the treatment of cancer and also in MDS. ATP-binding cassette (ABC) transporters are involved in the main mechanism that confers drug resistance to cells. Increased expression of drug resistance genes, such as MDR1, MRP1 and LRP, is involved with multi-drug resistance in MDS. The expression of these drug efflux transporters acts in synergy with other alterations, such as epigenetic events, increases in multidrug resistance in MDS. Methylation, the main epigenetic mechanism is widely explored in other hematological malignancies; however, in MDS, this mechanism is poorly investigated. Clinical trials evaluated or are under ongoing evaluation of drugs that abrogated ABC transporters action or reversed the abnormal methylation of some genes in MDS. In this report, we explore the data available in the field of drug resistance and methylation both in pediatric and adult MDS.
Keywords: myelodysplastic syndrome, multi-drug resistance, MDR1, LRP, methylation
Current Pharmaceutical Biotechnology
Title: Drug Resistance and Methylation in Myelodysplastic Syndrome
Volume: 8 Issue: 2
Author(s): D. O. Vidal, L. F. Lopes and E. T. Valera
Affiliation:
Keywords: myelodysplastic syndrome, multi-drug resistance, MDR1, LRP, methylation
Abstract: Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder that presents a poor survival for patients treated with standard therapies other than stem-cell transplantation. Multi-drug resistance (MDR) to simultaneous drugs used in chemotherapy is a major concern in the treatment of cancer and also in MDS. ATP-binding cassette (ABC) transporters are involved in the main mechanism that confers drug resistance to cells. Increased expression of drug resistance genes, such as MDR1, MRP1 and LRP, is involved with multi-drug resistance in MDS. The expression of these drug efflux transporters acts in synergy with other alterations, such as epigenetic events, increases in multidrug resistance in MDS. Methylation, the main epigenetic mechanism is widely explored in other hematological malignancies; however, in MDS, this mechanism is poorly investigated. Clinical trials evaluated or are under ongoing evaluation of drugs that abrogated ABC transporters action or reversed the abnormal methylation of some genes in MDS. In this report, we explore the data available in the field of drug resistance and methylation both in pediatric and adult MDS.
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Cite this article as:
Vidal O. D., Lopes F. L. and Valera T. E., Drug Resistance and Methylation in Myelodysplastic Syndrome, Current Pharmaceutical Biotechnology 2007; 8 (2) . https://dx.doi.org/10.2174/138920107780487483
DOI https://dx.doi.org/10.2174/138920107780487483 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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