title: Cytogenetics of long-term survivors of ETV6-RUNX1 fusion positive acute lymphoblastic leukemia.
abstract: This study describes the cytogenetics of 33 children with ETV6-RUNX1 positive acute lymphoblastic leukemia (ALL) who had been in continuous complete remission for a minimum of 8.8 years [median event-free survival (EFS) 10.9 years]. The results were compared with a published series of 16 fusion positive patients treated on the same childhood ALL trial, who had relapsed (median EFS, 2.3 years). Interphase fluorescence in situ hybridization (FISH) at diagnosis showed deletion of the second ETV6 signal from all fusion positive cells in 45% of the long-term survivors but in none of the relapsed patients, whereas patients with mixed populations with retained or lost second signals were more frequent among those who had relapsed (69%) than the long-term survivors (21%). Interphase populations with two fusion signals in 18% of the long-term survivors and 31% of relapsed patients were smaller in the long-term survivors (median, 4% of total cells) than in the relapsed patients (median, 84%). The additional copy of chromosome 21 in 30% of long-term survivors and in 69% of relapsed patients was a derived chromosome 21 in 20% and 55% of patients, respectively. Metaphase FISH for 26 long-term survivors and 15 relapsed patients revealed complex karyotypes in both groups. Variant translocations involved different chromosome arms between the long-term survivors and relapsed patients. It appears that the two groups have some distinguishing cytogenetic features at the time of diagnosis, which may provide pointers to relapse that are worthy of more detailed study.
authors.affiliation: Leukaemia Research Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK.
authors.forename: Zoë J
authors.initials: ZJ
authors.lastname: Konn
authors.forename: Mary
authors.initials: M
authors.lastname: Martineau
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bown
authors.forename: Sue
authors.initials: S
authors.lastname: Richards
authors.forename: John
authors.initials: J
authors.lastname: Swansbury
authors.forename: Polly
authors.initials: P
authors.lastname: Talley
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Wright
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005500:Follow-Up Studies; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics*; D017741:Survivors; D013997:Time Factors; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human