A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line

The use of 2-DE coupled with a MS approach resulted in the identification of 36 differentially expressed proteins. Differential mRNA levels of leucine-rich PPR motif-containing (LRPPRC) protein, minichromosome maintenance complex component 7 (MCM7) and ATP-binding cassette sub-family B (MDR/TAP) member 1 (ABCB1) were capable of defining samples from CML patients as responsive or resistant to therapy.Through the data presented in this work, we show the relevance of MDR to IM therapy. In addition, our proteomic approach identified candidate actors involved in resistance, which could lead to additional information on BCR-ABL-independent molecular mechanisms.Chronic myeloid leukemia (CML) is a myeloproliferative disease, and the BCR-ABL constitutive tyrosine kinase (TK), an oncoprotein, serves as a marker of this condition. This oncoprotein is responsible for the pathogenesis of CML and is the primary molecular target for disease therapy [1]. Although CML treatment has improved with the development of imatinib mesylate (IM, Glivec？, Gleevec - Novartis), a TK inhibitor, some patients fail to respond to this therapy [2]. Resistance to treatment was first related to BCR-ABL-dependent mechanisms, such as mutations of the BCR-ABL kinase site. However, mutations are not seen in all patients who are resistant to IM treatment. This suggests that other resistance mechanisms occur in these patients. Among these mechanisms, known as BCR-ABL-independent mechanisms, is the multidrug resistance (MDR) phenotype [3-9]. MDR is known to be the major cause of failure in cancer treatment and has a multifactorial origin. It is related to the expression of ATP-binding cassette (ABC) family transporters such as P-glycoprotein (Pgp-ABCB1), breast cancer related protein (BCRP-ABCG2) and multiresistance protein (MRP-ABCC1) [10,11]. Despite the identification and knowledge of ABC transporters, the resulting pathways involved in MDR rise in IM resistance, causing leukemic cells to become resistant