Clinical Relevance of RUNX1 and CBFB Alterations in Acute Myeloid Leukemia and Other Hematological Disorders

The translocation t(8;21), leading Metzeler, K.H. Bloomfield, C.D. to a fusion between the RUNX1 gene and the RUNX1T1 locus, was the first chromosomal translocation identified in cancer. Since the first description of this balanced rearrangement in a patient with acute myeloid leukemia (AML) in 1973, RUNX1 translocations and point mutations have been found in various myeloid and lymphoid neoplasms. In this chapter, we summarize the currently available data on the clinical relevance of core binding factor gene alterations in hematological disorders. In the first section, we discuss the prognostic implications of the core binding factor translocations RUNX1-RUNX1T1 and CBFB-MYH11 in AML patients. We provide an overview of the cooperating genetic events in patients with CBF-rearranged AML and their clinical implications, and review current treatment approaches for CBF AML and the utility of minimal residual disease monitoring. In the next sections, we summarize the available data on rare RUNX1 rearrangements in various hematologic neoplasms and the role of RUNX1 translocations in therapy-related myeloid neoplasia. The final three sections of the chapter cover the spectrum and clinical significance of RUNX1 point mutations in AML and myelodysplastic syndromes, in familial platelet disorder with associated myeloid malignancy, and in acute lymphoblastic leukemia.