title: miR expression profiling at diagnosis predicts relapse in pediatric precursor B-cell acute lymphoblastic leukemia.
abstract: Our aim was to identify miRNAs that can predict risk of relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Following high-throughput miRNA expression analysis (48 samples), five miRs were selected for further confirmation performed by real time quantitative PCR on a cohort of precursor B-cell ALL patients (n = 138). The results were correlated with clinical parameters and outcome. Low expression of miR-151-5p, and miR-451, and high expression of miR-1290 or a combination of all three predicted inferior relapse free survival (P = 0.007, 0.042, 0.025, and <0.0001, respectively). Cox regression analysis identified aberrant expression of the three miRs as an independent prognostic marker with a 10.5-fold increased risk of relapse (P = 0.041) in PCR-MRD non-high risk patients. Furthermore, following exclusion of patients harboring IKZF1 deletion, the aberrant expression of all three miRs could identify patients with a 24.5-fold increased risk to relapse (P < 0.0001). The prognostic relevance of the three miRNAs was evaluated in a non-BFM treated precursor B-cell ALL cohort (n = 33). A significant correlation between an aberrant expression of at least one of the three miRs and poor outcome was maintained (P < 0.0001). Our results identify an expression profile of miR-151-5p, miR-451, and miR-1290 as a novel biomarker for outcome in pediatric precursor B-cell ALL patients, regardless of treatment protocol. The use of these markers may lead to improved risk stratification at diagnosis and allow early therapeutic interventions in an attempt to improve survival of high risk patients.
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Smadar
authors.initials: S
authors.lastname: Avigad
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Iedan R N
authors.initials: IR
authors.lastname: Verly
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Lebel
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Oshrit
authors.initials: O
authors.lastname: Kordi
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Shichrur
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Ohali
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Hameiri-Grossman
authors.affiliation: Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.affiliation: Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cloos
authors.affiliation: Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Fronkova
authors.affiliation: Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Drorit
authors.initials: D
authors.lastname: Luria
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yona
authors.initials: Y
authors.lastname: Kodman
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Mirsky
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dafna
authors.initials: D
authors.lastname: Gaash
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Marta
authors.initials: M
authors.lastname: Jeison
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Galia
authors.initials: G
authors.lastname: Avrahami
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Elitzur
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Gilad
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel.|Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D011379:Prognosis; D012008:Recurrence
chemical_list: D035683:MicroRNAs