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

Proteome Science

Research

Luciana Pizzatti¹  Daniela Pinto¹  André Mencalha¹  Bárbara Du Rocher¹  Eliana Abdelhay²  Stephany Corrêa³ 

[1] Laboratório Célula-Tronco, Divisão de Laboratórios do CEMO, Instituto Nacional de Câncer, Rio de Janeiro, Brazil;Laboratório Célula-Tronco, Divisão de Laboratórios do CEMO, Instituto Nacional de Câncer, Rio de Janeiro, Brazil;Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratório Célula-Tronco, Divisão de Laboratórios do CEMO, Instituto Nacional de Câncer, Rio de Janeiro, Brazil;Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto Nacional de Câncer, Praça da Cruz Vermelha, n° 23, 6° andar, ala C, CEMO, Laboratório Célula-Tronco, CEP, 20230130, Rio de Janeiro, RJ, Brazil;

关键词: Imatinib mesylate;    Chronic myeloid leukemia;    LRPPRC;    MCM7;    Proteome;    Mass spectrometry;   

DOI  :  10.1186/1477-5956-10-23

 received in 2011-10-23, accepted in 2012-03-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAlthough chronic myeloid leukemia (CML) treatment has improved since the introduction of imatinib mesylate (IM), cases of resistance have been reported. This resistance has been associated with the emergence of multidrug resistance (MDR) phenotype, as a BCR-ABL independent mechanism. The classic pathway studied in MDR promotion is ATP-binding cassette (ABC) family transporters expression, but other mechanisms that drive drug resistance are largely unknown. To better understand IM therapy relapse due to the rise of MDR, we compared the proteomic profiles of K562 and Lucena (K562/VCR) cells.ResultsThe 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.ConclusionsThrough 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.

【 授权许可】

CC BY   
© Corrêa et al; licensee BioMed Central Ltd. 2012