Journal of pediatric hematology/oncology · 2003
Reduced folate carrier and dihydrofolate reductase expression in acute lymphocytic leukemia may predict outcome: a Children's Cancer Group Study.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод пока не подготовлен
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Levy Adam S, Sather Harland N, Steinherz Peter G, Sowers Rebecca, La Mei, Moscow Jeffrey A, Gaynon Paul S, Uckun Fatih M, Bertino Joseph R, Gorlick Richard, Children's Cancer Group Study
Аннотация
PURPOSE: Methotrexate is a major component of current treatment regimens for children with acute lymphocytic leukemia (ALL). Potential mechanisms of methotrexate resistance include impaired drug uptake, decreased drug retention, and dihydrofolate reductase (DHFR) amplification. The purpose of this study was to assess whether reduced folate carrier (RFC) and DHFR expression in untreated leukemic blasts correlated with outcome.
METHODS: Quantitative real-time RT-PCR was used to measure RFC and DHFR mRNA expression in leukemic blasts from 40 newly diagnosed patients with ALL obtained in a blinded fashion from Children's Cancer Group studies.
RESULTS: Low RFC expression at diagnosis correlated significantly with an unfavorable event free survival. Surprisingly, low, not high, DHFR expression correlated significantly with an unfavorable event-free survival. Proliferative cell nuclear antigen (PCNA) expression demonstrated a weak inverse relationship between sample PCNA and DHFR or RFC expression, suggesting that DHFR and RFC expression may be markers for factors other than drug resistance.
CONCLUSIONS: These results suggest that impaired transport may be an important mechanism of intrinsic methotrexate resistance in ALL, and DHFR expression also may be an important prognostic factor in ALL. Additional studies are necessary to clarify the mechanism for the correlation of low DHFR expression with poor outcome.
METHODS: Quantitative real-time RT-PCR was used to measure RFC and DHFR mRNA expression in leukemic blasts from 40 newly diagnosed patients with ALL obtained in a blinded fashion from Children's Cancer Group studies.
RESULTS: Low RFC expression at diagnosis correlated significantly with an unfavorable event free survival. Surprisingly, low, not high, DHFR expression correlated significantly with an unfavorable event-free survival. Proliferative cell nuclear antigen (PCNA) expression demonstrated a weak inverse relationship between sample PCNA and DHFR or RFC expression, suggesting that DHFR and RFC expression may be markers for factors other than drug resistance.
CONCLUSIONS: These results suggest that impaired transport may be an important mechanism of intrinsic methotrexate resistance in ALL, and DHFR expression also may be an important prognostic factor in ALL. Additional studies are necessary to clarify the mechanism for the correlation of low DHFR expression with poor outcome.
Предметные рубрики MeSH
Antimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsBiological TransportCarrier ProteinsChildChild, PreschoolDisease-Free SurvivalDrug Resistance, NeoplasmEnzyme InhibitorsFemaleFolate Receptors, GPI-AnchoredGene Expression ProfilingGene Expression Regulation, LeukemicHumansInfantMaleMethotrexateNeoplastic Stem CellsPrecursor Cell Lymphoblastic Leukemia-LymphomaProliferating Cell Nuclear AntigenReceptors, Cell SurfaceTetrahydrofolate Dehydrogenase