CBFβ/MYH11 Translocation Probe Dual Fusion

The fusion gene MYH11/CBFβ is created by the inversion inv(16)(p13q22), 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.

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 abnormalities.

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 which patients, the split signal may be lost. Variant rearrangements are t(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 prognosis.

The breakpoints occur in intron 5 of CBFβ‚ and intron 5 of MYH11 and 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 and 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.

The CBFβ probe, labelled in red, covers a 617 kb region of 16q22, extending from 298 kb 5’ of CBFβ to 246 kb beyond the 3’ terminus of the gene. For MYH11, the probe covers 610 kb region of 16p13. This probe set will detect the inv(16) fusion and the variants.