title: Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion.
abstract: Pediatric acute myeloid leukemia (AML) is a heterogeneous disease, characterized by different collaborating karyotypic and molecular abnormalities, which are used in risk group stratification. In ∼20% of the pediatric AML cases a specific genetic aberration is still unknown. Minimally differentiated myeloid leukemia or FAB-type M0 is a rare morphological subtype of AML. The translocation t(10;17)(p15;q21) is described to be recurrent in minimally differentiated AML, but the involved genes and location of the breakpoints have so far not been identified. In this study, we show that this translocation results in an in-frame translocation fusing exon 12 of the tumor suppressor gene ZMYND11 to exon 3 of the chromatin protein MBTD1, encoding a protein of 1,054 amino acids, while the reciprocal fusion product is predicted to lack a productive start codon. Gene expression profiling of the leukemic cells showed high HOXA expression. ZMYND11, also known as BS69, is a tumor suppressor that specifically recognizes H3K36me3, which is linked to aberrant HOXA expression in leukemogenesis. Aberrant expression of the genes involved in this fusion may thus contribute to the HOXA-phenotype observed with gene expression profiling.
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Pediatric Oncology/Hematology, Rotterdam, The Netherlands.
authors.forename: Jasmijn D E
authors.initials: JD
authors.lastname: de Rooij
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Pediatric Oncology/Hematology, Rotterdam, The Netherlands.|Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.affiliation: Pediatric Immunology, Hemato-Oncology and Stem Cell Transplantation, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wouter J W
authors.initials: WJ
authors.lastname: Kollen
authors.affiliation: Dutch Childhood Oncology Group (DCOG), The Hague, the Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Sonneveld
authors.affiliation: Pediatric Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.affiliation: Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.|Dutch Working Group on Hemato-Oncologic Genome Diagnostics, Rotterdam, The Netherlands.
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Pediatric Oncology/Hematology, Rotterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Fornerod
authors.affiliation: Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Pediatric Oncology/Hematology, Rotterdam, The Netherlands.
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002648:Child; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C546112:MBTD1 protein, human; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C094763:ZMYND11 protein, human