Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia

Abstract

Childhood acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia. Specifically, ALL is a malignant disorder of the lymphoid progenitor cells, with a peak incidence among children aged 2-5 years. The t(12;21)(p13;q22) translocation occurs in 25 % of childhood B cell precursor ALL. In this study, bone marrow samples were obtained from 165 patients with childhood ALL. We analyzed the t(12;21) translocation and other related abnormalities using the fluorescent in situ hybridization (FISH) technique with the ETV6(TEL)/RUNX1(AML1) ES dual color translocation probe. Conventional cytogenetic analyses were also performed. ETV6 and RUNX1 related chromosomal abnormalities were found in 42 (25.5 %) of the 165 patients with childhood ALL. Among these 42 patients, structural changes were detected in 33 (78.6 %) and numerical abnormalities in 9 (21.4 %). The frequency of FISH abnormalities in pediatric ALL cases were as follows: 8.5 % for t(12;21)(p13;q22) ETV6/RUNX1 fusion, 6.0 % for RUNX1 amplification, 3.0 % for tetrasomy/trisomy 21, 1.8 % for ETV6 deletion, 1.21 % for ETV6 deletion with RUNX1 amplification, 1.21 % for ETV6 amplification with RUNX1 amplification, 0.6 % for polyploidy, 0.6 % for RUNX1 deletion, and 0.6 % for diminished ETV6 signal. The most common structural abnormality was the t(12;21) translocation, followed by RUNX1 amplification and ETV6 deletion, while the most commonly observed numerical abnormality was trisomy 21.

Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group

“…The proportion of children with ETV6/RUNX1-positive ALL in this study was 18.2% of ALL in the same period, which is similar to the results in Korea ( 16 ) (23.1%), Greece ( 17 ) (22.7%), Czech Republic ( 18 ) (22%), Turkey ( 19 ) (25.5%), and the United States ( 20 ) (12.8%), but higher than India ( 14 ) (6%), Mexico ( 15 ) (9.6%) and lower than Iran ( 21 ) (34.9) and Europe ( 22 ) (31.5%). The exact reasons for the differences in rates across countries are unclear, and we speculate that they may be due to ethnic differences.…”

“…Flow cytometry (FCM)-MRD was analyzed according to previous literature from French multicenter study groups for pediatric and adult ALL ( 14 , 15 ). MRD was analyzed at the central protocol laboratory—the hematology labs of Kingmed Diagnostics Corperation by Kaluza software or Cellquest software.…”

Old and New Prognostic Markers in Pediatric ALL

“…In this issue, Aydin et al [1] compare conventional cytogenetics with FISH and RT-PCR testing for t(12;21)(p13;q22) in pediatric B-acute lymphoblastic leukemia (ALL) patients. This disease represents an outstanding example, together with APML and CML, of modern medicine's triumph over hematological malignancies using a combination of monitoring and risk-adapted therapeutic strategies [2].…”

“…ALL and characterized by late relapses with excellent chemosensitivity [2,7]. From a laboratory perspective, as the Aydin paper [1] illustrates, FISH probes for the ETV6/RUNX1 fusion also enable presumptive identification of aneuploidies of chromosomes 12 or 21 as well as ETV6or RUNX1 deletions or amplifications. The poor prognostic intra-chromosomal amplification of chromosome 21 (iAMP21) is also detectable by this modality [7,8].…”

Análise de expressão da metiltransferase SETD4 em leucemia linfoide aguda e sua relação com a leucemogênese

“…ETV6-RUNX1, antes conhecido como TEL-AML1, é o gene de fusão resultante da translocação entre a banda 13 do braço curto do cromossomo 12 e a banda 22 do braço longo do cromossomo 21. Esta é a mais frequente alteração citogenética encontrada em casos de B-LLA, correspondendo a cerca de 25% deles, e representa um marcador de bom prognóstico (14). Sabe-se também que, por si só, a t(12;21)(p13;q22) não provoca o aparecimento de leucemia sozinha, de modo que são necessárias mutações adicionais para tanto (13,15).…”