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Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in patients with acute myeloid leukemia

10.1016/j.xcrm.2023.101108

Affiliations
Allison L Boyd, Justin Lu, Cameron G Hollands, Lili Alsostovar, Shiva Murali, Jennifer C Reid, Wendy Ye, Sean Vandersluis, Paige Johnson, Amro ElRafie, Deanna P Porras, Dimetri Xenocostas, Andrew Leber, Brian Leber, Ronan Foley, Michael Trus, Tobias Berg, Eri Kawata, Anargyros Xenocostas, Mickie Bhatia

DOI: 10.1016/j.xcrm.2023.101108

Abstract
We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.

Keywords
acute myeloid leukemia, cancer stem cell, colony forming unit, leukemic progenitor cell, leukemic stem cell, prognostic, survival, xenotransplantation

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