RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis

Abstract

RUNX1 is a transcription factor that regulates critical processes in many aspects of hematopoiesis. RUNX1 is also integral in defining the definitive hematopoietic stem cell. In addition, many hematological diseases like myelodysplastic syndrome and myeloproliferative neoplasms have been associated with mutations in RUNX1. Located on chromosomal 21, the RUNX1 gene is involved in many forms of chromosomal translocations in leukemia. t(8;21) is one of the most common chromosomal translocations found in acute myeloid leukemia (AML), where it results in a fusion protein between RUNX1 and ETO. The RUNX1-ETO fusion protein is found in approximately 12% of all AML patients. In this review, we detail the structural features, functions, and models used to study both RUNX1 and RUNX1-ETO in hematopoiesis over the past two decades.

Figure 1

RUNX1 isoforms and genomic locus. (A) The RUNX1 genomic locus on chromosome 21 is shown with the location of the proximal and distal promotors and exons based on the National Center for Biotechnology Information Nucleotide database. (B) The three main transcriptional isoform of RUNX1 are shown. RUNX1a is consists of exons 4a through 8. RUNX1b consists of exons 4a through 10, but excludes exon 8. RUNX1c includes exons 1 through 3 and exons 4b through 10, but also excludes exon 8. (C) The three main RUNX1 isoforms are shown with the Runt homology domain shaded.

Figure 2

RUNX1 protein domains and interaction partners. The RUNX1b isoform is shown with the major domains listed above and interaction partners listed below.

Figure 3

RUNX1-ETO protein domains and interaction partners. The full length RUNX1-ETO is shown with the major domains listed above and interaction partners listed below.