In the current study, we first applied proteomic approach to identify galectin-1 as a candidate of MDR1 modulators for mediating drug resistance in CML cells by comparison of the protein profiles among a model system of leukemia cell lines with a gradual increase of MDR1 expression and drug resistance, and further explored the mechanisms of galectin-1 acting as a novel MDR1 modulator contributing to functional resistance against the cytotoxic drugs. Here, LGALS1 is linked to leukemia.