We have collected clinical data for 235 childhood ALL patients, for whom samples taken at the time of diagnosis were also broadly characterized with respect to MTX resistance. However, the relation between MTX resistance and long-term clinical outcome of ALL has not been shown previously. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent in tumor cells, have been classified as determinants of MTX resistance. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblastic leukemia (ALL). Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death.
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