Figure 3.Suggested models of AML transformation. Three suggested scenarios of step by step transformation in human AML, leading from a normal cell (orange) to a premalignant cell (pink) and, finally, to a malignant cell (brown) with clonal expansion: Scenario 1; both the initial transforming incident and following mutations leading to clonal expansion occur at the level of multipotent precursors; Scenario 2; the initial transforming incident occurs at the level of multipotent precursors, whiles the cooperating mutational event leading to clonal expansion occurs at the level of committed myeloid progenitors; and Scenario 3; both initial and following mutations occur at the level of committed myeloid precursors [2].|@|~(^,^)~|@|(A) Chimeric antigen receptor (CAR). CARs include of an extracellular domain created by attaching the light and heavy chain variable regions of a monoclonal antibody with a linker to form a single-chain Fv (scFv) molecule. The scFv is attached via a hinge region to the transmembrane and intracellular receptor portion. The three generation of CARs has been shown. (B) Innovative CAR design. Suicide gene strategies are investigated as control mechanisms for better toxicity management of CAR T cells. The inducible caspase 9 (iCasp9) is one of the example in this field. The details are explained in Hoffman et al. (2019). In brief, when the small molecule is administered, iCasp9 domains activate apoptosis independently of CAR activation. Bispecific CARs bear two linked scFV within one CAR construct, whereas dual CARs express two different antigen-specific CARs. TCR-mimic (TCRm) CARs directing the scFv domain against a peptide- human leukocyte antigen (HLA) complex have been developed for addressing the HLA [5].|@|~(^,^)~|@|CAR T-cell therapy for AML.

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