CBFβ, 16q22, Red
MYH11, 16p13.11, Green
The CBFβ probe, labelled in red, covers a 617kb region, within 16q22.1 and includes the CBFβ gene. The MYH11 probe, labelled in green, covers a 621kb region within 16p13.11 and includes the MYH11 gene.
The CBFβ (core-binding factor subunit beta) gene is located at 16q22.1 and the MYH11 (myosin heavy chain 11) gene is located at 16p13.11. The inversion inv(16)(p13.11q22.1) and the translocation t(16;16) (p13.11;q22.1) give rise to the CBFβ-MYH11 fusion gene.
Acute myeloid leukaemias with inv(16)(p13.11q22.1) or t(16;16)(p13.11;q22.1) form a recognised disease entity according to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia1. These rearrangements are frequently found in patients with a myelomonocytic subtype with increased bone marrow eosinophils, AML FAB (French-American-British classification) type M4Eo, and are found in 5-8%1 of all AMLs. Cases of therapy- related AML may also have this rearrangement1,2.
CBFB-MYH11 rearrangements are classed as a favourable cytogenetic risk group in patients with AML3,4.
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 chimeric 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.
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