title: Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia.
abstract: BACKGROUND
  The t(9;22) and t(4;11) chromosomal translocations, which generate the BCR-ABL and MLL-AF4 fusion genes, define high-risk subtypes of acute lymphoblastic leukemia in adults. However, the prognostic impact of other rarer fusion genes is less well established in adult acute lymphoblastic leukemia than in the childhood form.
  
  
  METHODS
  In the context of the German Multicenter Therapy Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) we used reverse transcriptase polymerase chain reaction to investigate 441 cases of BCR-ABL- and MLL-AF4-negative B-precursor acute lymphoblastic leukemia for the TCF3-PBX1 (E2A-PBX1) and ETV6-RUNX1 (TEL-AML1) fusion transcripts generated by the t(1;19)(q23;p13.3) and t(12;21)(p13;q22) translocations. Both are well-known molecular alterations in pediatric acute lymphoblastic leukemia in which they have favorable prognostic implications.
  
  
  RESULTS
  We identified 23 adult patients with TCF3-PBX1 and ten with ETV6-RUNX1. In contrast to previous reports we found no significant difference in overall survival between TCF3-PBX1-positive and -negative patients. At 2 years after diagnosis all the ETV6-RUNX1-positive patients were alive and in continuous complete remission, but their long-term outcome was negatively affected by late relapses. TCF3-PBX1-positive patients exhibited a characteristic CD34(-)/CD33(-) and mostly cyIg(+) immunophenotype. ETV6-RUNX1 only occurred in patients under 35 years old and was associated with a significantly lower white blood count.
  
  
  CONCLUSIONS
  In contrast to previous suggestions, adult patients with TCF3-PBX1-positive acute lymphoblastic leukemia do not appear to have a worse outcome than their negative counterparts. ETV6-RUNX1-positive patients had a very favorable performance status during the first few years but their long-term survival was negatively affected by late relapses. Both groups of patients are characterized by distinct clinicobiological features which facilitate their diagnostic identification.
authors.affiliation: Med Klinik für Hämatologie/Onkologie Hindenburgdamm 30, 12200 Berlin, Germany. thomas.burmeister@charite.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.forename: Lars
authors.initials: L
authors.lastname: Fischer
authors.forename: Daniela
authors.initials: D
authors.lastname: Hubert
authors.forename: Annette
authors.initials: A
authors.lastname: Sindram
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000293:Adolescent; D000328:Adult; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000628:therapy; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D016044:Fusion Proteins, bcr-abl; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C113855:MLL-AF4 fusion protein, human; C543638:TCF3-PBX1 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C406060:abl-bcr fusion protein, human