title: mRNA expression profile of multidrug-resistant genes in acute lymphoblastic leukemia of children, a prognostic value for ABCA3 and ABCA2.
abstract: Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, including ABCA2, ABCA3, ABCB1/MDR1, MRP1/ABCC1, MRP3/ABCC3, ABCG2/BCRP, and the intracellular transporter MVP/LRP, in childhood ALL, and to evaluate their association with response to therapy. Some genes in the present research are being studied for the first time in Iran. Using quantitative real-time PCR, we evaluated 27 children with ALL at diagnosis and 15 children with normal bone marrow. The status of response to therapy was assessed one year after the onset of therapy through investigating the IgH/TCRγ gene rearrangements. Our findings indicate a considerable and direct relationship between mRNA expression levels of ABCA2, ABCA3, MDR1, and MRP1 genes and positive minimal residual disease (MRD) measured after one year of treatment. Statistical analysis revealed that expression of these genes higher than the cutoff point will raise the risk of MRD by 15-, 6.25-, 12-, and 9-fold, respectively. No relationship was found between of MVP/LRP, MRP3 and ABCG2 genes expression and ALL prognoses. Considering the direct and significant relationship between the increased expression of ABCA2, ABCA3, MDR1, and MRP1 genes and positive risk of MRD in children with ALL, evaluating the expression profile of these genes on diagnosis may identify high risk individuals and help plan a more efficient treatment strategy.
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Rahgozar
authors.affiliation: Department of Paediatric-Oncology; Sayed ol Shohada Hospital; Isfahan University of Medical Sciences; Isfahan, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moafi
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Abedi
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Mansureh
authors.initials: M
authors.lastname: Entezar-E-Ghaem
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Jamal
authors.initials: J
authors.lastname: Moshtaghian
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghaedi
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Esmaeili
authors.affiliation: Division of Cell and Molecular Biology; Department of Biology; Faculty of Science; University of Isfahan; Isfahan, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Montazeri
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C418186:ABCA2 protein, human; C441524:ABCA3 protein, human
keywords: ABC transporter; acute lymphoblastic leukemia; minimal residual disease; multidrug resistance