title: RUNX1 amplification in lineage conversion of childhood B-cell acute lymphoblastic leukemia to acute myelogenous leukemia.
abstract: Amplification of RUNX1 (alias AML1) is a recurrent karyotypic abnormality in childhood acute lymphoblastic leukemia (ALL) that is generally associated with a poor outcome. It does not occur with other primary chromosomal abnormalities in acute ALL. AML1 amplification in acute myelogenous leukemia (AML) is a rare secondary event described mainly in therapy-related cases. AML1 amplification was found in a 13-year-old patient with AML M4/M5 leukemia that occurred 5 years after she had been diagnosed with common B-cell ALL. Conventional cytogenetic, fluorescent in situ hybridization (FISH), and polymerase chain reaction methods revealed no other chromosomal change expected to occur in a disease that we assumed to be a secondary leukemia. Due to the lack of cytogenetic data from the diagnostic sample, we developed a new approach to analyze the archived bone marrow smear, which had been stained previously with May-Grünwald-Geimsa by the FISH method. This analysis confirmed that in addition to t(12;21), AML1 amplification and overexpression existed already at the time the diagnosis was made. The chromosomal changes, however, were found in different clones of bone marrow cells. While the first course of chemotherapy successfully eradicated the cell line with the t(12;21), the second cell line with AML1 amplification remained latent during the time of complete remission and reappeared with a different immunophenotype.
authors: Department of Haematology, University Medical Centre Ljubljana, Zaloska 7, 1000 Ljubljana, Slovenia. helena.podgornik@kclj.si
authors: Helena
authors: H
authors: Podgornik
authors: Marusa
authors: M
authors: Debeljak
authors: Darja
authors: D
authors: Zontar
authors: Peter
authors: P
authors: Cernelc
authors: Veronika Velensek
authors: VV
authors: Prestor
authors: Janez
authors: J
authors: Jazbec
mesh_terms: D000293:Adolescent; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D012008:Recurrence; D012074:Remission Induction; D014407:Tumor Cells, Cultured
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human