磷酸化 Crkl 降低水平与慢性髓性白血病患者细胞中最低的 P-糖蛋白活性水平相关。

Phosphorylated Crkl reduction levels are associated with the lowest P-glycoprotein activity levels in cells from chronic myeloid leukemia patients.

机构信息

Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Brazil.

出版信息

Leuk Res. 2013 Dec;37(12):1711-8. doi: 10.1016/j.leukres.2013.09.021. Epub 2013 Sep 29.

DOI:10.1016/j.leukres.2013.09.021

PMID:24210993

Abstract

ABCB1/P-glycoprotein (Pgp) and ABCG2/BCRP overexpression have been described as related to imatinib resistance in chronic myeloid leukemia (CML). We showed in CML cells from 55 patients that Pgp activity was more frequently detected than BCRP activity (p=0.0074). Imatinib-induced Crkl phosphorylated protein (pCrkl) reduction was more pronounced in K562 (Pgp-negative) than in K562-Lucena (Pgp-positive) CML cell line. Expressive pCrkl reduction levels after in vitro imatinib treatment was observed in samples from patients exhibiting lower Pgp activity levels compared with patients exhibiting higher Pgp activity levels (p=0.0045). Pgp activity in association with pCrkl reduction levels might help to distinguish between imatinib-resistant and imatinib-sensitive CML cells.

摘要

ABCB1/P-糖蛋白（Pgp）和 ABCG2/BCRP 的过表达与慢性髓性白血病（CML）中的伊马替尼耐药有关。我们在 55 名患者的 CML 细胞中表明，Pgp 活性的检出频率高于 BCRP 活性（p=0.0074）。伊马替尼诱导的 Crkl 磷酸化蛋白（pCrkl）减少在 K562（无 Pgp）比 K562-Lucena（有 Pgp）CML 细胞系中更为明显。与 Pgp 活性较高的患者相比，Pgp 活性较低的患者的样本在体外伊马替尼治疗后观察到更明显的 pCrkl 减少水平（p=0.0045）。Pgp 活性与 pCrkl 减少水平的关联可能有助于区分伊马替尼耐药和伊马替尼敏感的 CML 细胞。