Transporter expression profiled in childhood T cell acute lymphoblastic leukemia

10-30-2006

Recent research from Germany has chronicled the expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia (T-ALL).

"A major issue in the treatment of T-ALL is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters. The majority of these proteins have not yet been examined in T-ALL," wrote T. Efferth and colleagues, German Cancer Research Center.

"Using a newly developed microarray for the simultaneous quantification of 38 ABC transporter genes, we observed a consistent overexpression of ABCA2/ABCA3 in clinical samples of ALL. Therefore, we analyzed the association of these two genes with drug resistance.

"Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells," wrote the researchers.

"To study the causal relationship of ABCA2/A3 overexpression with drug resistance, we applied RNA interference (RNAi) technology. RINAi specific for ABCA2 or ABCA3 led to a partial decrease of expression in these two ABC transporters. Upon cotreatment of RNAi for ABCA2 with methotrexate and vinblastine, a partial decrease of ABCA2 expression as well as a simultaneous increase of ABCA3 expression was observed.

"Vice versa, ABCA3 RNAi plus drugs decreased ABCA3 and increased ABCA2 expression. This indicates that down-regulation of one ABC transporter was compensated by the up-regulation of the other. Application of RNAi for both ABCA2 and ABCA3 resulted in a more efficient reduction of the expression sensitization of cells to cytostatic drugs was achieved," the investigators continued.

The scientists concluded, "ABCA2 and ABCA3 are expressed in many T-ALL and contribute to drug resistance."

Efferth and colleagues published their study in Molecular Cancer Therapeutics (Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia. Mol Cancer Ther, 2006;5(8):1986-1994).

For additional information, contact T. Efferth, German Cancer Research Center, M070, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

Publisher contact information for the journal Molecular Cancer Therapeutics is: American Association of Cancer Research, 615 Chestnut St., 17th Floor, Philadelphia, PA 19106-4404, USA.

Keywords: Heidelberg, Germany, Cancer Therapy, Doxorubicin, Drug Resistance, Leukemia, Methotrexate, Multidrug Resistance, ATP-Binding, Cassette Transporters, Transporter Genes, Vinblastine.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2006, Hematology Week via NewsRx.com.