Fig. 4.

Simple diagrammatical display of de novo AML clonal evolution and distinction of gene signatures between therapy‐naïve cells and chemotherapy‐treated cells. (A) The leukaemia‐initiating (founding) clone contains AML pathogenic somatic mutations; among the founding clone, one subclone is eradicated by the chemotherapy whilst the other with relapse‐initiating mutations accumulated further mutations to evolve into a dominant clone at relapse. HSC (adapted from [13]). (B) Molecular signatures, such as therapy‐naïve leukaemia stem cell (LSC) signatures, LSC17 [85] and stemness [84], leukaemic regeneration cell signature [27] and chemoresistance signature [26], are discrete between therapy‐naïve LSCs and leukaemic cells after exposure to chemotherapy during the course of disease in adults. These signatures permit the identification of therapy‐naïve LSCs and the discrimination between impending relapse vs durable disease‐free survival in human AML patients during remission states. The status of these signatures in relapse patients is not yet well defined.