Transcription factor PU.1 (PU.1) (PU.1)

Transcription factor PU.1, encoded by the SPI1 gene, is a member of the ETS family and serves as a master regulator of hematopoiesis. It is critical for the lineage commitment and maturation of myeloid cells, such as monocytes and granulocytes, as well as B-lymphocytes (UniProt P17947). In many cases of acute myeloid leukemia (AML), PU.1 activity is suppressed or dysregulated, leading to a block in cell differentiation and promoting leukemogenesis (PubMed PMID: 30643213). The PU.1–DNA complex represents a specific therapeutic target where small molecules, such as heterocyclic diamidines, bind to the DNA recognition site to modulate or inhibit PU.1's transcriptional activity (PubMed PMID: 24511211). Targeting this interaction aims to restore normal differentiation or induce apoptosis in malignant cells. However, because PU.1 is vital for normal immune function and blood cell production, achieving selectivity for leukemic cells while avoiding systemic hematopoietic toxicity remains a significant therapeutic challenge (PubMed PMID: 27551068).

Other names

SPI1Spleen focus forming virus proviral integration oncogene spi1SFPI1Hematopoietic transcription factor PU.1SPI-1

Inhibition of the PU.1-DNA binding interface through competitive binding at the DNA minor groove or the ETS-binding site (PubMed PMID: 24511211).