Treatment of resistant leukemia is a challenge for the researchers, mainly due to the complexity of this phenomenon. Resistant cells often presented cross-resistance to unrelated agents; in this way the sensibility of the MDR tumor cells to antineoplastic agents can decrease significantly. In this context, the establishment of new biosensors and targets in resistant cells represents an important factor to improve the diagnosis and therapy efficiency. The goal of this work was to demonstrate the effects of protein phosphatases inhibitors (okadaic acid, a serine/threonine phosphatase (PP2A) inhibitor, and pervanadate, a protein tyrosine phosphatase (PTP) inhibitor) on the metabolism of resistant human myeloid leukemia (LUCENA) cells. For this purpose, the cells were treated for 72h with the phosphatase inhibitors and the cell viability was analyzed through MTT reduction and trypan blue exclusion. Apoptosis induction was evaluated by flow cytometry using annexin FITC as a marker. We observed that protein phosphatase inhibitors caused apoptosis in LUCENA cells. Okadaic acid presented toxic effect on LUCENA cells at nM range (20-100), while pervanadate showed the same effect at μM range (20-80).  Our results suggest that protein phosphatases exert important function in LUCENA cells and the inhibition of these enzymes could be a potential therapeutic strategy. Finally, this work provided new insights about the biological activities of protein phosphatases in resistant cells and suggested that these enzymes are interesting candidates in the treatment of leukemia.