The investigators at St. Jude made their discoveries using bone marrow cells harvested from mice that either carried the gene for BCRP or lacked this gene. In conditions of low oxygen, the HSCs from mice that carried the gene for BCRP multiplied normally, apparently because they were able to rid themselves of excess heme. Similar cells from mice that lacked this gene -- and thus could not protect themselves from excess heme -- replicated only half as effectively as normal cells.

When HSCs from mice carrying the BCRP gene were kept at normal oxygen levels and given the anti-leukemic drug mitoxantrone, 40 percent survived, apparently because they used BCRP to rid themselves of that drug. However, if HSCs from mice lacking the BCRP gene were exposed to mitoxantrone under the same conditions, none of the cells survived.

Other authors of the study were Partha Krishnamurthy, Sheng Zhou, Kelly E. Mercer and Brian P. Sorrentino (St. Jude); Douglas D. Ross, Takeo Nakanishi and Kim Bailey-Dell (University of Maryland School of Medicine); and Balazs Sarkadi (National Medical Center, Budapest Hungary). This work was supported in part by NIH, a Cancer Center support grant, a VA Merit Review Grant, ALSAC and a Howard Hughes International Scholarship.

St. Jude Children's Research Hospital