Organista-Nava Jorge, Gómez-Gómez Yazmín, Del Moral-Hernandez Oscar, Illades-Aguiar Berenice, Gómez-Santamaria Jazmin, Rivera-Ramírez Ana Bertha, Saavedra-Herrera Mónica Virginia, Jimenez-López Marco Antonio, Leyva-Vázquez Marco Antonio
Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, México.
Laboratorio de Virología, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39090, México.
Oncol Lett. 2019 Sep;18(3):3115-3127. doi: 10.3892/ol.2019.10650. Epub 2019 Jul 22.
The present study analyzed the mRNA expression levels of genes involved in the transport and metabolism of methotrexate (MTX) (RFC1, ABCC1, ABCB1, GGH, FPGS, ATIC, TS, MTHFR, MTRR, MS and MTHFD1) in patients with acute leukemia (AL). The expression levels of the examined genes were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with AL (ALL:50/AML:19) and 66 healthy individuals. The mRNA expression levels of RFC1, MS, MTRR, MTHFR and ABCB1 were decreased (P<0.05), while those of GGH, FPGS, TS and MTHFD1 (P<0.05) were overexpressed in patients with AL. Patients with high mRNA levels of GGH (OR=4.28, 95% CI=1.29-14.14), TS (OR=7.14, 95% CI 1.84-27.81), MTHFR (OR=4.81, 95% CI=1.31-17.64), ABCB1 (OR=4.61, 95% CI=1.33-15.97) and ABCC1 (OR=5.50, 95% CI=1.12-27.06) had a higher chance of relapse. Interestingly, high mRNA levels of RFC1 are a protective factor in the risk of AL relapse (OR=0.22, 95% 0.06-0.80). The results of the present study indicated that deregulation of folate pathway gene expression is associated with poor prognosis in AL and that the expression levels of these markers could serve as novel molecular targets for the treatment of patients with AL.
本研究分析了急性白血病（AL）患者中参与甲氨蝶呤（MTX）转运和代谢的基因（RFC1、ABCC1、ABCB1、GGH、FPGS、ATIC、TS、MTHFR、MTRR、MS和MTHFD1）的mRNA表达水平。通过逆转录定量聚合酶链反应（RT-qPCR）分析了AL患者（急性淋巴细胞白血病：50例/急性髓细胞白血病：19例）和66名健康个体中检测基因的表达水平。AL患者中RFC1、MS、MTRR、MTHFR和ABCB1的mRNA表达水平降低（P<0.05），而GGH、FPGS、TS和MTHFD1的mRNA表达水平（P<0.05）过表达。GGH（OR=4.28，95%CI=1.29-14.14）、TS（OR=7.14，95%CI 1.84-27.81）、MTHFR（OR=4.81，95%CI=1.31-17.64）、ABCB1（OR=4.61，95%CI=1.33-15.97）和ABCC1（OR=5.50，95%CI=1.12-27.06）mRNA水平高的患者复发几率更高。有趣的是，RFC1的高mRNA水平是AL复发风险的保护因素（OR=0.22，95%0.06-0.80）。本研究结果表明，叶酸途径基因表达失调与AL预后不良相关，这些标志物的表达水平可作为治疗AL患者的新分子靶点。
