We therefore hypothesized that the engraftment of the endogenous SIRPα domain, which has a low affinity towards CD47 [16], onto a mAb targeting CD33 with high affinity, would result in a molecule that specifically recognizes and binds to AML cells via CD33 and locally blocks the CD47-SIRPα pathway. The gene discussed is SIRPA; the disease is acute myeloid leukemia.