Analysis of ETV6/AML1 abnormalities in acute lymphoblastic leukaemia: incidence, alternative spliced forms and minimal residual disease value
Autor: | R Codrington, Christine J. Harrison, SM Hart, H. G. Prentice, Letizia Foroni, G R Jalali, A. V. Hoffbrand, Michael Potter, H E O'Connor, Paola Carrara, Mary Papaioannou |
---|---|
Rok vydání: | 2001 |
Předmět: |
Male
medicine.medical_specialty Neoplasm Residual Adolescent Oncogene Proteins Fusion Molecular Sequence Data Chromosomal translocation Biology Gastroenterology Fusion gene Exon hemic and lymphatic diseases Acute lymphocytic leukemia Internal medicine Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Proto-Oncogene Proteins medicine Humans Amino Acid Sequence Child neoplasms Chromosome 12 Base Sequence Proto-Oncogene Proteins c-ets Reverse Transcriptase Polymerase Chain Reaction Incidence Cytogenetics Infant Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Minimal residual disease DNA-Binding Proteins Repressor Proteins ETV6 Alternative Splicing Child Preschool Core Binding Factor Alpha 2 Subunit Cancer research Female Transcription Factors |
Zdroj: | British journal of haematology. 111(4) |
ISSN: | 0007-1048 |
Popis: | The t(12;21)(p13;q22) translocation, resulting in the fusion of the ETV6 and AML1 genes, occurs in 20-25% of paediatric B-lineage acute lymphoblastic leukaemias (ALL). The identification of the fusion product has important prognostic and therapeutic implications as the translocation has been associated with a favourable clinical outcome. The aim of this study was threefold: (i) to assess the frequency and clinical association of the fusion gene in patients with and without a cytogenetically detectable chromosome 12 and/or 21 abnormality or failed cytogenetic results, (ii) to characterize alternative forms of ETV6/AML1 transcripts, and (iii) to use ETV6/AML1 as a molecular marker for the investigation of minimal residual disease (MRD). ETV6/AML1 fusion was detected in 22 (39%) of 56 cases studied by reverse transcriptase polymerase chain reaction (RT-PCR). ETV6/AML1 fusion was found in nine out of 16 (56%) cases with a cytogenetically visible chromosome 12 abnormality, but also in nine out of 29 patients (31%) without a chromosome 12 abnormality or patients with failed cytogenetics (four out of 11 patients, 36%), making this the most common cytogenetic abnormality in childhood ALL. Alternatively spliced ETV6/AML1 forms were investigated in 14 of the positive patients. Exon 5 of ETV6 was fused in frame to all AML1 exons, except exon 4. Fusion to exon 6 of AML1 resulted in one amino acid change. The presence of ETV6/AML1 was associated with a lower white blood cell count (Student's t-test; P = 0.009) and common (c)ALL phenotype (chi(2) test; P > 0.001), but no better disease-free survival. Our study shows that (i) RT-PCR is the most effective approach for the detection of t(12;21) in childhood ALL, (ii) the association of ETV6/AML1 and chromosome 12 and/or 21, seen in 56% of our cases, further confirms existing data, (iii) overall survival of patients with t(12;21) was not better than other cytogenetics groups, and (d) MRD analysis using ETV6/AML1 fusion is specific, but not sensitive enough to avoid false negative results. |
Databáze: | OpenAIRE |
Externí odkaz: |