title: Overexpression of SORCIN is a Prognostic Biomarker for Multidrug-Resistant Pediatric Acute Lymphoblastic Leukemia and Correlates with Upregulated MDR1/P-gp.
abstract: BACKGROUND
  Multidrug resistance is one of the major causes of treatment failure in pediatric acute lymphoblastic leukemia (ALL), and SORCIN is an intracellular calcium modulator protein. The current study was designed to investigate the in vitro and in vivo relationships between the expression levels of SORCIN: in tumor cell lines and children with ALL; its possible correlation with MDR1/P-glycoprotein (P-gp), a multidrug resistance-related gene; and response to therapy.
  
  
  METHODS
  Childhood T-lymphoblastic leukemia (CCRF-CEM) cell lines resistant to methotrexate (MTX) were developed. Patient studies were performed by including 30 children with ALL at diagnosis, 3 children with bone marrow relapse, and 15 children with no symptoms of cancer. The mRNA expression profiles of SORCIN and MDR1/P-gp was assessed using quantitative polymerase chain reaction (qPCR). Minimal residual disease (MRD) was measured in the patient population, a year following the initial therapy using qPCR.
  
  
  RESULTS
  Cell line data analyses showed a positive correlation between SORCIN mRNA levels and resistance to MTX. The difference between patient and control groups for SORCIN expression levels was not significant. However, patients with a negative response to therapy showed an increase in SORCIN mRNA levels (up to 6.8-fold) compared with those with negative MRD. In addition, the results demonstrated a significant positive correlation between SORCIN and MDR1/P-gp gene expression levels.
  
  
  CONCLUSIONS
  The current study introduces, for the first time, a possible prognostic value of SORCIN in childhood ALL, which may be correlated with MDR1/P-gp gene expression in these patients.
authors.affiliation: 1 Department of Biology, Faculty of Science, University of Isfahan , Isfahan, Iran .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Dabaghi
authors.affiliation: 1 Department of Biology, Faculty of Science, University of Isfahan , Isfahan, Iran .
authors.forename: Soheila
authors.initials: S
authors.lastname: Rahgozar
authors.affiliation: 1 Department of Biology, Faculty of Science, University of Isfahan , Isfahan, Iran .
authors.forename: Jamal
authors.initials: J
authors.lastname: Moshtaghian
authors.affiliation: 2 Department of Pediatric-Hematology-Oncology, Sayed-ol-Shohada Hospital, Isfahan University of Medical Sciences , Isfahan, Iran .
authors.forename: Alireza
authors.initials: A
authors.lastname: Moafi
authors.affiliation: 1 Department of Biology, Faculty of Science, University of Isfahan , Isfahan, Iran .
authors.forename: Marjan
authors.initials: M
authors.lastname: Abedi
authors.affiliation: 1 Department of Biology, Faculty of Science, University of Isfahan , Isfahan, Iran .
authors.forename: Elnaz
authors.initials: E
authors.lastname: Pourabutaleb
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D054316:Biomarkers, Pharmacological / Q000097:blood; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; C503113:SRI protein, human