Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Drug resistance and methylation in myelodysplastic syndrome. 1743 Jan 55

Acute myeloid leukemia (AML) is a clonal disorder of the hematopoietic stem cell, typical of the elderly, with a median age of over 60 years at diagnosis. In AML, older age is one of the strongest independent adverse prognostic factor, associated with decreased complete response rate, worse disease-free and overall survival, with highest rates of treatment related mortality, resistant disease and relapse, compared to younger patients. Outcomes are compromised in older patients not only by increased comorbidities and susceptibility to toxicity from therapy, but it is now recognized that elderly AML has peculiar biologic characteristics with a negative impact on treatment response.In older individuals prolonged exposure to environmental carcinogens may be the basis for similarities to therapy-related myeloid malignancies (t-MN), which result from toxic effects of previous cytotoxic treatments on hematopoietic stem cells. Age is itself a risk factor for t-MN, which are more frequent in elderly patients, where also a shorter latency between treatment of primary tumor and t-MN has been reported. t-MN following chemotherapy with alkylating agents and elderly AML frequently present MDS-related cytogenetic abnormalities, including complex or monosomal karyotype, and a myelodysplastic phase preceding the diagnosis of overt leukemia. Similarly, t-MN and elderly-AML share common molecular abnormalities, such as reduced frequency of NPM1, FLT3 and CEBPA mutations and increased MDR1 expression.Given the unfavorable prognosis of elderly and t-MN and the similar clinical and molecular aspects, this is a promising field for implementation of new treatment protocols including alternative biological drugs.
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PMID:Similarities and differences between therapy-related and elderly acute myeloid leukemia. 2222 Feb 49


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