Breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MRX) or placenta ABC protein (ABC-P), is the second member of the ABCG subfamily of ABC transport proteins (gene symbol ABCG2). Transfection and enforced expression of BCRP in drug-sensitive cells confers resistance to mitoxantrone, doxorubicin, daunorubicin and topotecan. In this study the expression of BCRP gene was measured using TaqMan real-time PCR in 59 children with newly diagnosed AML. Nine patients were also analyzed in relapse. The median of BCRP gene expression was more than 10 times higher in patients who did not achieve remission after the first phase of chemotherapy (n ‫؍‬ 24) as compared to patients who did achieve remission at this stage (n ‫؍‬ 21; P ‫؍‬ 0.012). In first relapse the expression of the BCRP gene was higher than at diagnosis (P ‫؍‬ 0.038). Although high levels of BCRP gene expression were more frequent in subtypes of AML with a favorable prognosis, we found that within both risk groups (high and low risk), patients who expressed high levels of BCRP had a worse prognosis (P ‫؍‬ 0.023). Our results strongly suggest that the expression of the BCRP gene reduces the response to chemotherapy in AML and that BCRP expression is higher at the time of relapse.

Summary. The breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MXR) or placenta ABC protein (ABC-P), is the second member of the ABCG subfamily of ABC transport proteins (gene symbol ABCG2). BCRP has been detected in acute myeloid leukaemia and in breast, colon and gastric cancer but there has been no reports regarding BCRP expression in acute lymphoblastic leukaemia (ALL). We report the first results of BCRP expression in childhood ALL. Sixty-seven children (47 initial stage, 20 relapses) with ALL were analysed for BCRP gene expression by TaqMan real-time polymerase chain reaction. The expression of BCRP in mononuclear cells obtained from the bone marrow (BM) and peripheral blood (PB) of healthy donors was also investigated. There was no relationship between BCRP expression and age, sex, initial blast cell count, prednisolone response or BM response on d 15 and 33. Patients with T-lineage ALL showed a lower expression of BCRP (P ¼ 0AE044). Kaplan-Meier analysis of the relapse-free interval showed no prognostic significance of BCRP expression when different levels of BCRP expression were used as cut-off points. No significant difference in expression of BCRP mRNA was measured between initialstage and relapsed-stage ALL or between normal MNC obtained from BM and ALL patients. The results indicate a low expression of BCRP in childhood ALL. Relationships between BCRP and clinical, molecular or in vivo resistance characteristics of the patients were not observed.Keywords: multidrug resistance, BCRP, prognosis, ALL.Overexpression of proteins which belong to the adenosidetriphosphate-binding cassette (ABC) superfamily of transporters have been shown as an important cause of cellular drug resistance (Riordan & Ling, 1989;Cole et al, 1992;Sauerbrey et al, 1994; van den Heuvel-Eibrink et al, 2000). In this context, the most extensively studied members of these proteins are P-170 glycoprotein (P-170) and the multidrug resistance-related protein (MRP). Several studies showed that drug transporters other than P-170 or MRP may also be important for resistance. The most recently identified member of this family of ABC transporters is the breast cancer-related protein (BCRP), which was isolated from multidrug-resistant MCF7/ADRVp breast cancer cells (Ross et al, 1999;Rocchi et al, 2000). The BCRP is encoded by the ABCG2 Gene which was mapped to chromosome 4 (Allikmets et al, 1998). The protein consists of 655 amino acids with a molecular weight of 72AE6 kDa (Doyle et al, 1998). Further characterization of this protein showed BCRP as a half transporter (Miyake et al, 1999). Transfection and overexpression of BCRP in sensitive MCF7 cells confers resistance to mitoxantrone, doxorubicin, daunomycin and various camptothecin analogues (Allen et al, 1999). High expression for BCRP has been found in different human gastric, colon, breast, ovarian and bladder cancer cells while expression of BCRP in normal tissue is low (Maliepaard et al, 1999;Ross et al, 1999). Preliminary results showed that BCR...

Background Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the

Leukemia ER, Janka-Schaub GE, Creutzig U, Veerman AJP. Cellular drug resistance profiles in childhood acute myeloid leukemia: differences between FAB-types and comparison with acute lymphoblastic leukemia.Leukemia be introduced into the therapy of childhood AML with great caution and only if they prove to have a strong beneficial effect in adult AML.

Use of peridural anaesthesia, nulliparity, high birth weight and induction of labour were risk factors for unsuccessful vaginal breech delivery requiring an unplanned caesarean section. Awareness of these risk factors is useful when counselling women who are considering a vaginal breech delivery.