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BACKGROUND Dysregulations of the WNT pathway are implicated in the malignant transformation of different types of neoplasia's. WNT7A is expressed in normal peripheral lymphocytes but in the tumoral counterpart is decreased. Furthermore, treatment of leukemic cells with recombinant WNT7A decreases proliferation suggesting its possible use as a therapeutic biomolecule. The aim of this study was to evaluate the concomitantly action of WNT7A and different chemotherapeutic agents over proliferation and cell death of leukemia/lymphoma derived cell lines. METHODS Ectopic expression of WNT7A was induced in CEM and BJAB cell lines by using a lentiviral system. RNA expression was analyzed by microarrays and qPCR, and protein expression was determined by Western Blot. Cell proliferation was measured by cell counting, metabolic activity by WST-1 assay, cell death and DNA content by flow cytometry. RESULTS WNT7A ectopic expression was shown to decrease cell proliferation but the apoptosis rate of leukemic cells was not altered. Moreover, these cells acquired resistance to doxorubicin, vincristine and MG-132. Cell cycle analysis reveals a decrease in G1 and an increase in S and G2 phases with a further upregulation of senescence associated genes. Microarray analysis reveals that most of gene expression changes were related to cancer and metabolic associated pathways. All those changes appear to be independent of the WNT canonical pathway regulation. CONCLUSION WNT7A negatively regulates cell proliferation in leukemic cell lines but promotes resistance to chemotherapeutic agents by inducing a senescence like phenotype independently of the WNT canonical pathway.