Corebinding Factor Leukemia

Two categories in the WHO classification of AML, namely AML with t(8;21)(q22;q22)/AML1(RUNX1)-ETO(CBFA2T1) and AML with abnormal BM eosinophils and inv(16) (p 13q22) or t(16;16)(p13;q22)/CBFB-MYH11, are characterized by chromosomal aberrations that rearrange genes encoding different subunits of core-binding factor (CBF). These AML types are collectively referred to as CBF AML. The CBF complex is a heterodimeric transcription factor, composed of a and P subunits, which regulates transcription of several genes involved in hematopoietic differentiation, including cytokines such as interleukin-3 (IL-3), gran-ulocyte-macrophage colony-stimulating factor (GM-CSF), and the macrophage colony-stimulating factor receptor (M-CSFR). The CBFa subunit, encoded by the RUNX1 gene (also known as AML1 and CBFA2), harbors a DNA-binding domain, whereas the CBFp subunit does not directly bind DNA, but physically associates with CBFa and stimulates its DNA-binding activity, thereby regulating transcription.22 The intact CBF complex is critical for normal hematopoiesis; disruption of either of its subunits directly contributes to leukemic transformation.

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