To clarify the mechanism of progression and acquired drug resistance of leukemia, we searched for an overexpressed gene in drug-resistant leukemia cells and identified an approximately 5-kb transcript by using the subtraction method. The nucleotide sequence of the gene was highly homologous to those of human endogenous retrovirus (HERV) transcripts. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the gene was overexpressed in cells from 6 childhood acute lymphoblastic leukemia patients (60%) but not in bone marrow cells at remission. Peripheral blood mononuclear cells from normal controls (n=11) and bone marrow cells from non-leukemia patients (n=13) did not express the gene. These findings indicate that the gene may play a role in leukemogenesis and may be a novel leukemia marker. Further studies on the functional role of the gene are needed.