In groundbreaking research, scientists at the Tisch Cancer Institute at Mount Sinai in New York, New York, generated patient-derived induced pluripotent stem cell (iPSC) models that represent all major genetic classes of human acute myeloid leukemia (AML), including the survival rate.1

The iPSC models “exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation,” wrote Kotini and colleagues in their report published in Blood Cancer Discovery.1

These findings are expected to pave the way for significant developments in both AML research and studies using iPSCs in other human cancers.1

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“We have said for years that we have been able to effectively cure leukemia in mice, most likely because the leukemia models in mice have been overly simplistic,” stated Mikkael Sekeres, MD, professor of medicine and chief of hematology at the University of Miami School of Medicine in Miami, Florida, and chair of the American Society of Hematology Committee on Communications.

“A key to understanding the biology of AML and being able to treat it effectively is the ability to faithfully recapitulate this complicated cancer in a pre-clinical model, especially one that could be used for accurate drug testing,” Dr Sekeres explained in an interview with Hematology Advisor. “This is not easy, as AML itself arises from a series of genetic mutations that occur over time, and the pressures that lead to one subsequent mutation or another can result in the clinical manifestations of leukemia differing from one patient to another.”

Although advances in humanized mouse models have enabled in vivo xenotransplantation of human AML cells, capturing the chromosomal abnormalities of AML is difficult in the context of animal models.2

Previous research aiming to reprogram human cancer cells to iPSCs has either been unsuccessful or unclear in terms of the degree of resemblance to their primary counterparts, thus limiting progress in the understanding of these diseases and optimal treatment strategies.1

In this study, however, the “authors were able to reproduce human versions of AML in mice, including the complex genetic diversity, which sets the stage for better pre-clinical drug testing to lead to improved therapies for AML in the future,” Dr Sekeres said.