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Coexpression of Multiple ABC‐Transporters is Strongly Associated with Treatment Response in Childhood Acute Myeloid Leukemia
Author(s) -
Bartholomae Stephan,
Gruhn Bernd,
Debatin KlausMichael,
Zimmermann Martin,
Creutzig Ursula,
Reinhardt Dirk,
Steinbach Daniel
Publication year - 2016
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25785
Subject(s) - medicine , abcg2 , atp binding cassette transporter , oncology , myeloid leukemia , multidrug resistance associated protein 2 , drug resistance , cancer research , pharmacology , transporter , gene , biology , genetics
Background To analyze whether expression of ABC‐transporters is associated with remission rate and long‐term outcome in a prospective clinical trial of childhood acute myeloid leukemia (AML). Procedure The expression of four ABC‐transporter genes ( ABCA3 encoding drug transporter ABCA3, ABCB1 encoding multidrug resistance protein 1, ABCC3 encoding multidrug resistance‐associated protein 3, and ABCG2 encoding breast cancer resistance protein) was measured by TaqMan real time polymerase chain reaction in pretreatment samples from 112 children with AML. Patients were treated according to multicenter study AML‐Berlin, Frankfurt, Munich (BFM) 2004. Results ABCC3 ( P = 0.009) and ABCG2 ( P = 0.03) were associated with a lower chance to achieve remission after the first course of chemotherapy. ABCC3 was associated with lower relapse free survival (RFS) ( P = 0.02). ABCG2 was expressed at higher levels in subtypes of AML with favorable outcome but within standard‐ and high‐risk patients, it was associated with poor outcome ( P = 0.02). A strong association was observed between the number of overexpressed ABC‐transporters and the chance to achieve remission ( P = 0.01) or the chance of RFS ( P < 0.001). Conclusions The intensive treatment regimen of AML‐BFM 2004 did not readily overcome drug resistance caused by ABC‐transporters. Inhibition of ABC‐transporters might be particularly useful in patients who express multiple of these genes.