title: MicroRNA-106b~25 cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia.
abstract: The most important reason for therapy failure in pediatric acute myeloid leukemia (AML) is relapse. In order to identify miRNAs that contribute to the clonal evolution towards relapse in pediatric AML, miRNA expression profiling of 127 de novo pediatric AML cases were used. In the diagnostic phase, no miRNA signatures could be identified that were predictive for relapse occurrence, in a large pediatric cohort, nor in a nested mixed lineage leukemia (MLL)-rearranged pediatric cohort. AML with MLL- rearrangements are found in 15-20% of all pediatric AML samples, and reveal a relapse rate up to 50% for certain translocation partner subgroups. Therefore, microRNA expression profiling of six paired initial diagnosis-relapse MLL-rearranged pediatric AML samples (test cohort) and additional eight paired initial diagnosis-relapse samples with MLL-rearrangements (validation cohort) was performed. A list of 53 differentially expressed miRNAs was identified of which the miR-106b~25 cluster, located in intron 13 of MCM7, was the most prominent. These differentially expressed miRNAs however could not predict a relapse in de novo AML samples with MLL-rearrangements at diagnosis. Furthermore, higher mRNA expression of both MCM7 and its upstream regulator E2F1 was found in relapse samples with MLL-rearrangements. In conclusion, we identified the miR-106b~25 cluster to be upregulated in relapse pediatric AML with MLL-rearrangements.
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Lonneke J
authors.initials: LJ
authors.lastname: Verboon
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Askar
authors.initials: A
authors.lastname: Obulkasim
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jasmijn D E
authors.initials: JD
authors.lastname: de Rooij
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Katsman-Kuipers
authors.affiliation: Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Sonneveld
authors.affiliation: Department of Hematology, Hopital Saint- Louis, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: Department of Pediatric Hematology/Oncology, 2nd Medical School, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.affiliation: Clinic for Pediatrics III, University Hospital Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.affiliation: Paediatric Oncology/Haematology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cloos
authors.affiliation: Paediatric Oncology/Haematology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Jan-Henning
authors.initials: JH
authors.lastname: Klusmann
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Christian Michel
authors.initials: CM
authors.lastname: Zwaan
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Fornerod
authors.affiliation: Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands.|Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D063646:Carcinogenesis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D060965:Clonal Evolution; D015331:Cohort Studies; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism; D005810:Multigene Family; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014178:Translocation, Genetic; D015854:Up-Regulation
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C497422:KMT2A protein, human; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7
keywords: MLL; acute myeloid leukemia; miR-106b~25; relapse