BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia

Steinbach, Daniel; Sell, Wieland; Voigt, Astrid; Hermann, J; Zintl, F; Sauerbrey, Axel

doi:10.1038/sj.leu.2402541

Cited by 188 publications

(127 citation statements)

References 14 publications

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“…21 Alternatively, mechanisms other than MDR1 might be responsible for the development of clinical drug resistance. [22][23][24] Cure rate in AML has improved with intensive induction and postremission therapy with optimized timing. The best results were obtained with the most drug-intensive regimens.…”

Section: Maintenance Therapymentioning

confidence: 99%

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Pérel¹,

Auvrignon²,

Leblanc³

et al. 2005

Leukemia

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From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucé mie Aiguë Myé loblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 6074 and 4874%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 5274% for non-allografted patients and 5777% for allografted patients (P ¼ NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MTÀ) than in patients randomized for MT (77.678 vs 5978%; P ¼ 0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.

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Section: Maintenance Therapymentioning

confidence: 99%

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Pérel¹,

Auvrignon²,

Leblanc³

et al. 2005

Leukemia

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“…In fact, some reports have shown an association between BCRP expression and a poor response to chemotherapy. For example, the expression of BCRP has been reported in leukemic cells (13) and solid tumors (14-16) from patients, and increased expression of BCRP has been implicated in resistance to induction therapy against childhood acute myeloid leukemia (17). Furthermore, it has been reported that levels of BCRP are higher in cases of hepatic metastasis after irinotecan-based chemotherapy than in cases of irinotecan-naive metastasis (18), and BCRP impacts clinical outcome in platinum-based chemotherapy for advanced non-small cell lung cancer (19).…”

Section: Introductionmentioning

confidence: 99%

Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo

Yamazaki

Nishiyama

Furuta

et al. 2011

Molecular Cancer Therapeutics

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Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38-resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1-mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRPtransduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy.

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“…5 However, the significance of BCRP in AML is unclear, possibly reflecting the use of different assays in different studies. [6][7][8][9][10][11][12][13] Little is known about the correlation between BCRP assays in AML. We studied expression of wild-type and mutant BCRP mRNA, expression of BCRP protein detected by the three available BCRP-specific monoclonal antibodies and function of BCRP in eight cell lines with different levels of BCRP-mediated resistance and in blasts from 31 untreated AML patients.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function

et al. 2004

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Data on breast cancer resistance protein (BCRP, MXR, ABCG2) expression in acute myeloid leukemia (AML) have been inconsistent, possibly due to use of different assays in different studies. BCRP mRNA was studied by the reverse-transcription polymerase chain reaction and BCRP protein expression (BXP-21, BXP-34 or anti-ABCG2 antibody, with anti-CD34 and anti-CD33) and function (fumitremorgin C modulation of mitoxantrone retention) by flow cytometry in eight cell lines and in pretreatment blasts from 31 AML patients. BCRP mRNA levels, antibody staining and function correlated strongly in cell lines (Pearson r values, 0.73-0.97), but not in AML samples. AML sample BCRP mRNA levels were between those in parental 8226 and 35-fold mitoxantrone-resistant 8226/MR20 cells in all but one case, and BCRP mRNA had the wild-type sequence at codon 482 in all. In AML, unlike in cell lines, BCRP protein expression or function, when present, was only detected in small subpopulations. BCRP mRNA and protein expression did not correlate, nor did staining with different BCRP antibodies, and function did not correlate with mRNA nor protein expression. Presence of BCRP only in subpopulations and discordance among BCRP measurements suggest complex biology of BCRP in AML and incomplete modeling by cell lines.

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BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia

Cited by 188 publications

References 14 publications

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit – multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group

Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo

Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function

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