Here, we describe distinct isoglycoforms of CD45 that function as E-selectin ligands on healthy human hematopoietic progenitor cells and on AML blasts, providing functional insights into CD45 structural biology that greatly extend our understanding regarding this definitional and ubiquitous cell surface marker of hematopoietic-lineage cells. This evidence concerns the gene PTPRC and acute myeloid leukemia.