title: Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome.
abstract: The 8p11 myeloproliferative syndrome (EMS) is a chronic myeloproliferative disorder molecularly characterized by fusion of various 5' partner genes to the 3' part of the fibroblast growth factor receptor 1 (FGFR1) gene at 8p, resulting in constitutive activation of the tyrosine kinase activity contained within FGFR1. EMS is associated with a high risk of transformation to acute myeloid leukemia (AML), but the mechanisms underlying the disease progression are unknown. In the present study, we have investigated a case of EMS harboring a t(8;22)(p11;q11)/BCR-FGFR1 rearrangement as well as a t(9;21)(q34;q22) at the time of AML transformation. FISH and RT-PCR analyses revealed that the t(9;21) leads to a fusion gene consisting of the 5' part of RUNX1 (exons 1-4) fused to repetitive sequences of a gene with unknown function on chromosome 9, adding 70 amino acids to RUNX1 exon 4. The t(9;21) hence results in a truncation of RUNX1. No point mutations were found in the other RUNX1 allele. The most likely functional outcome of the rearrangement was haploinsufficiency of RUNX1, which thus may be one mechanism by which EMS transforms to AML.
authors: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. helena.agerstam@med.lu.se
authors: Helena
authors: H
authors: Agerstam
authors: Henrik
authors: H
authors: Lilljebjörn
authors: Carin
authors: C
authors: Lassen
authors: Agneta
authors: A
authors: Swedin
authors: Johan
authors: J
authors: Richter
authors: Peter
authors: P
authors: Vandenberghe
authors: Bertil
authors: B
authors: Johansson
authors: Thoas
authors: T
authors: Fioretos
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D018076:DNA, Complementary; D018450:Disease Progression; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary; C493728:RUNX1 protein, human