Background:Acute myeloid leukemia (AML) is a clonal malignant disease of hematopoietic tissues that is defined by the accumulation of leukemic blast cells in the marrow resulting in hematopoietic failure.Among human peripheral blood cells,Cluster of Differentiation 96 (CD96) expression was observed on T and Natural Killer (NK) cells but not on the majority of B cells, monocytes, and granulocytes. In contrast to the role of CD96 participating in immune surveillance of tumors, CD96 itself was identified as a tumor marker. Indeed, well before first studies deciphered its functions, CD96 was reported to be upregulated in subpopulations of TAcute lymphoblastic leukemia (ALL) and AML. Increased expression of CD96 was shown in several subsequent studies to correlate with poor prognosis and enhanced resistance to chemotherapy. A promising treatment strategywould therefore be to sort out CD96-expressing stem cells before autologous transplantation of AML patients.