The TEL probe mix, labelled in red, contains a probe covering a 180kb region between the markers D12S845 and D12S89 and a second probe centromeric to the TEL (ETV6) gene, extending 168kb from the marker D12S1898. For AML1, there are two probes, labelled in green, one covering a 156kb region centromeric to the AML1 (RUNX1) gene, including the CLIC6 gene and a second probe covering a 169kb region, including the markers D21S1895 and D21S1921.
The cytogenetically-cryptic t(12;21)(p13;q22) translocation between ETV6 (ets variant 6) at 12p13 and RUNX1, (RUNX family transcription factor 1) at 21q22, results in the ETV6-RUNX1 chimeric fusion gene1.
The ETV6 and RUNX1 genes both encode transcription factors; ETV6 has been shown to be required for proper transcription during haematopoiesis within the bone marrow1,2. The ETV6-RUNX1 protein converts RUNX1 to a transcriptional repressor and causes overexpression of the erythropoietin receptor (EPOR) and activation of downstream JAK-STAT signaling1.
B-lymphoblastic leukaemia/lymphomas with t(12;21)(p13;q22) translocations form a recognised disease entity according to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia. This is the most common sub-group of childhood B-ALL accounting for about 25% of cases3. As the t(12;21)(p13;q22) translocation is cytogenetically-cryptic, FISH is an important diagnostic tool for this leukaemia4.
B-ALL with ETV6-RUNX1 is considered to have a favourable outcome with cure rates more than 90%3. Late relapses have been reported; these have been attributed to the presence of persistent preleukaemic clones that survived chemotherapy3,5.
ETV6 has also been shown to be deleted in some children with ALL, with loss of heterozygosity (LOH) of chromosome 12p12-13; these deletions often seen in the presence of ETV6-RUNX1 translocations6.
I first came across CytoCell FISH probes in a previous lab I worked in and I was struck by the quality of the products. Since this time, I have been recommending and introducing CytoCell probes across all application areas — now they are the primary FISH probes used in our lab. They have an excellent range of products and their ready-to-use reagent format saves considerable time.
Medical Technologist, University of Arizona Health Network, USA