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Polymorphisms in th...
Polymorphisms in the ABCB1 gene affect outcome and toxicity in Childhood Acute Lymphoblastic Leukemia
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- Gregers, Jannie (författare)
- Linköpings universitet,Klinisk farmakologi,Hälsouniversitetet
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- Gréen, Henrik (författare)
- Linköpings universitet,Klinisk farmakologi,Hälsouniversitetet
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- Jarle Christensen, Ib (författare)
- Rigshospital, Copenhagen, Denmark
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- Peterson, Curt (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Klinisk farmakologi,Hälsouniversitetet,Onkologiska kliniken US
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- Dalhoff, Kim (författare)
- Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark
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- Schroeder, Henrik (författare)
- Department of Pediatric, the University Hospital in Skejby, Aarhus, Denmark
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- Carlsen, Niels (författare)
- Department of Pediatric, the University Hospital in Odense, Denmark
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- Rosthoej, Steen (författare)
- Department of Pediatric, the University Hospital in Aalborg, Denmark
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- Lausen, Birgitte (författare)
- Department of Pediatric, Rigshospitalet, the University Hospital in Copenhagen, Denmark
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- Schmiegelow, Kjeld (författare)
- Institute of Gynecology, Obstetrics, and Pediatrics, The Medical Faculty, University of Copenhagen, Denmark
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(creator_code:org_t)
- 2012
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences pharmacokinetics in several anti-cancer drugs. We hypothesized that 1199G>A, 1236C>T, 2677G>A/T and 3435C>T variants of ABCB1 could affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL), since treatment includes known P-glycoprotein substrates and 3435C/T may affect methotrexate therapy. We studied 522 Danish children with ALL treated according to NOPHO ALL92 and ALL2000 protocols, 93% of all those eligible during 1992-2007. Risk of relapse was 2.9-fold increased for 41 patients with the 1199GA variant compared to 477 with 1199GG (p=0.001), and reduced by 61% and 40%, respectively for 421 patients with the 3435CT or 3435TT variants compared to 96 with 3435CC (overall p=0.02). Degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was higher in 71 patients with 3435TT variant (median nadirs: hemoglobin 3% and platelets 34/37% lower in3435CT/3435CC) compared to 160 patients with 3435CT/3435CC (Hemoglobin p=0.01 and platelets p<0.0001). We observed more liver toxicity after high-dose methotrexate in 109 patients with 3435CC variant versus 3435CT/TT (Median max alanineaminotransferase: 280 versus 142/111 U/L, p=0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms and efficacy and toxicity in childhood ALL.
Nyckelord
- Acute lymphoblastic leukemia; ABCB1; MDR1; P-glycoprotein; Polymorphism; Relapse; Toxicity
- MEDICINE
- MEDICIN
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