title: Interphase FISH on TEL/AML1 positive acute lymphoblastic leukemia relapses--analysis of clinical relevance of additional TEL and AML1 copy number changes.
abstract: OBJECTIVE
  TEL/AML1 (ETV6/RUNX1) fusion resulting from the translocation t(12;21)(p13;q22) constitutes the most common chimeric fusion gene in initial childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) (19-27%) and has been associated with good prognosis. Three secondary aberrations in TEL/AML1 positive ALL have been suspected to negatively influence outcome: deletion of the second TEL allele (T), gain of the second AML1 allele (A) and duplication of the derivative chromosome 21 (der(21), TA). Many studies have explored such aberrations in initial disease, while only few reports have investigated them in relapses.
  
  
  METHODS
  In this study, bone marrow samples from 38 children with relapsed TEL/AML1 RT-PCR positive and negative BCP-ALL were analyzed for these mutations by interphase fluorescence in situ hybridization and results were compared with published data.
  
  
  RESULTS
  In children with TEL/AML1 positive ALL relapse, additional (a) TEL loss, (b) combined AML1 and der(21) gain, (c) combined TEL loss and AML1 gain as well as (d) the occurrence of a subpopulation with the signal pattern 1T/3A/1TA appear to be related to higher peripheral blast counts (PBCs) at relapse diagnosis (a and d) or a tendency towards the occurrence of a subsequent relapse (b and c) (P-values <0.05).
  
  
  CONCLUSIONS
  Our data together with published results on TEL/AML1 positive ALL suggest that frequencies of additional TEL and AML1 mutations are, with the exception of loss of untranslocated TEL, higher in first relapses than in initial disease. They also show that it is important to consider combined mutations in the analysis of this leukemia entity.
authors: Department of Pediatric Oncology and Hematology, Otto-Heubner-Center for Pediatrics, Charité Campus Virchow-Klinikum, Berlin D-13353, Germany.
authors: Anita
authors: A
authors: Peter
authors: Thomas
authors: T
authors: Heiden
authors: Tillmann
authors: T
authors: Taube
authors: Gabriele
authors: G
authors: Körner
authors: Karl
authors: K
authors: Seeger
mesh_terms: D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy; D012008:Recurrence; D014178:Translocation, Genetic / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein