Deregulation of folate pathway gene expression correlates with poor prognosis in acute leukemia

• Published in: Experimental and therapeutic medicine Vol. 18; no. 3; pp. 3115 - 3127
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.09.2019; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Acute leukemia; Analysis; Blood; Bone marrow; Cancer; Cancer genetics; Confidence intervals; Dihydrofolate reductase; EDTA; Enzymes; Folic acid; Gene expression; Genes; Genetic aspects; Leukemia; Medical prognosis; Messenger RNA; Metabolism; Methotrexate; Mortality; Novels; Oncology; Physiological aspects; Polymerase chain reaction; Prognosis; RNA; Transcription (Genetics); Vitamin B; Mexico; United States > US; resistance to methotrexate; methotrexate; folate; relapse; acute leukemia
• ISSN: 1792-1074; 1792-0981; 1792-1082
• DOI: 10.3892/ol.2019.10650

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.