ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a distinct antigen-presenting phenotype.
The recently recognized translocation t(12;21)(p13;q22), which results in the ETV6-AML1 fusion product, is the most common genetic rearrangement found in childhood pre-B acute lymphoblastic leukaemia (ALL). It has been associated with a more favourable prognosis and a distinct immunophenotype in terms of myeloid and B cell-associated antigen expression. Using flow cytometry, we investigated whether the unique ETV6-AML1 phenotype extended to molecules associated with antigen presentation by analysing 50 diagnostic bone marrow samples from paediatric pre-B ALL patients. Reverse transcription polymerase chain reaction for the ETV6-AML1 fusion transcript was positive in 14 patients. ETV6-AML1-positive samples were characterized by a significantly higher expression of the co-stimulatory molecule CD40 (P < 0.0001), as well as a significantly higher class II HLA-DR mean channel fluorescence (P = 0.001). In contrast, CD86 expression was significantly lower on fusion-positive samples (P = 0.010) while there was no difference in expression of CD80 or major histocompatibility complex class I between ETV6-AML1-positive and -negative samples. This is the first observation in acute leukaemia that the distinct immunophenotype associated with specific translocations includes the expression of molecules associated with antigen presentation. In the case of ETV6-AML1 pre-B ALL, this characteristic immunophenotype may have implications for the immunogenicity of the leukaemic cells.
Alessandri
Angela J
AJ
Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia and British Columbia's Children's Hospital, Vancouver, BC, Canada.
Reid
Gregor S D
GS
Bader
Sharon A
SA
Massing
Bonnie G
BG
Sorensen
Poul H B
PH
Schultz
Kirk R
KR
D000938:Antigen-Presenting Cells / Q000276:immunology*; D019013:CD40 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D019013:CD40 Antigens; D050676:Core Binding Factor Alpha 2 Subunit; D006684:HLA-DR Antigens; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein