CBFβ/MYH11 Translocation, Dual Fusion
The fusion gene CBFβ (CBFB)/MYH11, created by the inversion inv(16)(p13.11q22.1), is found in 20% of AML M4 cases – in particular M4 with marked eosinophilia (M4eo) - and rarely, in M2, M5 and M4 without eosinophilia1.
Overall, abnormalities involving 16q22 are seen in 5-10% of AML1,2,3. Frequently, Central Nervous System (CNS) involvement develops, particularly in relapse. However, the complete remission rate is high and the prognosis is better than most of the AML associated abnormalities3.
The inversion may be missed in poor cytogenetic preparations. FISH probes for 16p13 often show a deletion within 16p13 in addition to the 16p13.11/16q22.1 rearrangement (~20% cases). In these patients, the split signal may be lost. Variant rearrangements are the (16;16)(p13;q22) and del(16)(q22). The latter is associated with previous MDS, older age, a complex karyotype and a worse prognosis. Additional abnormalities include +8, +22, del(7q) and +2, which confer no change to the prognosis1.
The breakpoints occur in intron 5 of CBFB and intron 5 of MYH11. The N-terminal of CBFB fuses to the C-terminal of MYH11 with its multimerisation domain. The resultant chimaeric protein reduces the amount of active CBF. An accumulation of CBFB-MYH11/CBFA multimers in the nucleus also occurs. CBFB regulates expression of certain ADP-Ribosylation Factors (ARFs) and other tumour suppressor genes (TSGs) and therefore the fusion protein is thought to repress TSG expression3.
1. Huret, inv(16)(p13q22); t(16;16)(p13;q22); del(16)(q22). Atlas Genet Cytogenet Oncol Haematol 1999
2. Heim and Mitelman, Wiley-Liss Inc. 1995
3. Monreno-Miralles et al., J Biol Chem 2005;280(48):40097-103
- Area of Interest*
This product is intended to be used on Carnoy’s solution (3:1 methanol/acetic acid) fixed haematological samples.
*Disease information supported by the literature and is not a reflection of the intended purpose of this product.