title: Poor outcome in a pediatric patient with acute myeloid leukemia associated with a variant t(8;21) and trisomy 6.
abstract: RUNX1T1/RUNX1 (formerly ETO/AML1) is a molecular marker that is usually associated with a favorable outcome in both pediatric and adult patients with acute myeloid leukemia (AML). We describe a 10-year-old girl with AML associated with an RUNX1T1/RUNX1 fusion. The patient's karyotype at the time of diagnosis was 46,X,-X,t(4;21;8)(q25;q22;q22),+6. She had an early relapse while being treated on a standard protocol and had significant difficulty in attaining a second remission. She subsequently underwent a matched related donor bone marrow transplant, but a second bone marrow relapse with extensive extramedullary disease followed on day +199. Cytogenetic analysis at second relapse showed evidence of clonal evolution in the form of a highly complex karyotype with numeric and structural abnormalities in addition to the t(4;21;8) and trisomy 6 detected in the diagnostic sample. Trisomy 6 is an uncommon cytogenetic abnormality in myeloid diseases. As a sole abnormality, it has been associated mainly with myelodysplastic syndrome and AML. The presence of this novel variant of t(8;21)(q22;q22) associated with trisomy 6 may have abrogated the usual favorable prognosis associated with RUNX1T1/RUNX1 in AML.
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, The Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903, USA. mkelly1@lifespan.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelly
authors.forename: Aurelia M
authors.initials: AM
authors.lastname: Meloni-Ehrig
authors.forename: Peter E
authors.initials: PE
authors.lastname: Manley
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Altura
mesh_terms: D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic / Q000235:genetics*; D014314:Trisomy / Q000235:genetics*
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein