A primary patient-derived model for investigating functional heterogeneity within the human Leukemic Stem Cell Compartment
Boutzen, H.; Chan-Seng-Yue, M.; Murison, A.; Mbong, N.; Wagenblast, E.; Arlidge, C.; Madani Tonekaboni, S. A.; Orouji, E.; Arruda, A.; Mitchell, A.; Notta, F.; Lupien, M.; Minden, M.; Kaufmann, K.; Dick, J.
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The ability of leukemic stem cells (LSC) to evade therapy and fuel leukemic progression causing relapse impedes therapeutic success in acute myeloid leukemia (AML). The LSC pool within a patient sample is not homogenous but comprises distinct LSC subsets that vary in self-renewal and propagation properties. The stemness programs that underlie LSC types are poorly understood since human LSC studies require primary patient samples where LSC numbers are low and isolation methods impure. To overcome these challenges, we developed a patient-derived AML model system (OCI-AML22) displaying a functionally, transcriptionally and epigenetically defined cellular hierarchy driven by functional LSCs that can be immunophenotypically identified and isolated. Through single cell and functional approaches, the OCI-AML22 LSC fraction was found to contain distinct LSCs that vary in proliferative and differentiation properties. OCI-AML22 represents a valuable resource to decipher mechanisms driving stemness and the multiple layers of heterogeneity within LSCs.
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