CBFß/MYH11 Translocation, Dual Fusion LPH022 - Detail

The fusion gene MYH11/CBFβ is created by the inversion inv(16)(p13;q22) found in 20% of AML M4 cases. In particular M4 with marked eosinophilia (M4eo) and rarely, in M2, M5 and M4 without eosinophilia. Overall, abnormalities involving 16q22 are seen in 5-10% of AML^1,2,3. Frequently CNS involvement develops particularly in relapse however the complete remission rate is high and the prognosis is better than most of the AML associated abnormalitie^3,4.The inversion may be missed in poor cytogenetic preparations. FISH probes for 16p13 often show a deletion within 16p13 in addition to the 16p13/16q22 rearrangement (~20% cases). In these patients, the split signal may be lost. Variant rearrangements are Additional abnormalities include +8, +22, del(7q) and +2 which confer no change to the prognosis. The breakpoints occur in intron 5 of CBFβ and intron 5 of MYH11. The N-terminal of CBFβ fuses to the C-terminal of MYH11 with its multimerization domain. The resultant chimeric protein reduces the amount of active CBF. An accumulation of CBFβ-MYH11/CBFα multimeres in the nucleus also occurs. CBFβ regulates expression of certain ADP-Ribosylation Factors (ARFs) and other TSGs and therefore the fusion protein is thought to repress TSG expression^2,3.

Reference:/Bibliographie/Literatur/Bibliografia

1. Heim and Mitelman 1995, Wiley-Liss inc.
2. Monreno-Miralles et al 2005 J Biol Chem, 280(48):40097-103.
3. Huret 1999 Atlas Genet Cytogenet Oncol Haematol June.
4. Le Beau et al 1996 Blood, vol 88, no 6, 1930-1935.