AML1 Breakapart Probe

The AML1 (CBFA2 or RUNX1) gene is the most frequent target of chromosomal rearrangements observed in human acute leukemia. The most common rearrangements are the TEL/AML and AML/ETO fusions.. The TEL(ETV6)/AML1fusion is brought about by the t(12;21)(p13;q22) translocation which is observed in 21% of childhood B-ALL cases Jamil, whilst the AML/ETOfusion is the result of the t(8;21)(q22;q22) translocation observed in ~40% of AML M2 and 7% of AML cases overall. Both of these rearrangements provide for a favourable outcome although the TEL/AML1 fusion is associated with late relapse.

The gene is also, however, rearranged in many other rare translocations including the partner chromosomes – 1, 2, 3, 4, 6, 9, 16, 20 and X

Rearrangements of the RUNX1 gene are not restricted to translocations, however. Using FISH, gene amplifications have also been found, essentially in childhood ALL and amplification of the gene has further been shown to be associated with poorer outcome in ALL, one mechanism for which is thought to be because of the overexpression of RUNX1 (AML1)

The Cytocell AML1 breakapart product has been designed to show gross changes in the AML1 gene so that prior knowledge of the partner chromosome(s) involved is not necessary as a rearrangement will be clearly visible in non-dividing cells as well as those at metaphase.

The AML1 probe mix contains a probe 151Kb 3’ of RUNX1 (including CLIC6) labelled in red and a second probe extending from intron 3 of RUNX1 to 51Kb beyond the 5’ end of the gene which is labelled in green.