26 April 2023

A new model has been created to allow improved research into acute myeloid leukaemia (AML) in the laboratory.

A research team, led by Dr Eirini Papapetrou, at Mount Sinai, New York, USA, set out to reprogramme human AML cells into induced pluripotent stem cell lines (iPSCs), to provide new accurate genetic models of AML.

This reprogramming approach has traditionally been technically challenging, leading to a low success rate. What’s more there is uncertainty over the similarity of the new cells to the original malignant ones.

However, the group has now developed a new reprogramming method which generated cells from 15 patients “representing all major genetic groups of acute myeloid leukaemia”. These AML-iPSCs are capable of recreating a variety of different haematopoietic cell types.

In the journal Blood Cancer Discovery last week, they reported that the cells “retain genetic fidelity and produce transplantable haematopoietic cells with hallmark phenotypic leukaemic features”.

When transplanted in immunodeficient mice, the resulting leukaemias “faithfully mimic the primary patient-matched xenografts”, the team adds. “The results and resources reported here can transform basic and preclinical cancer research of acute myeloid leukaemia and other human cancers.”

Dr Papapetrou said: “We show that these models are nearly identical to the leukaemias of the patients that they came from and thus are faithful models for acute myeloid leukaemia.

“Animal models do not provide accurate genetic models of AML, AML cells from the bone marrow or blood survive poorly outside of the body, and AML cell lines carry many additional genetic and karyotypic abnormalities that make them distinct from primary tumours.

“Our new models are groundbreaking tools that can uniquely empower leukaemia research.”


Kotini AG, Carcamo S, Cruz-Rodriguez N, Olszewska M, Wang T, Demircioglu D, Chang CJ, Bernard E, Chao MP, Majeti R, Luo H, Kharas MG, Hasson D, Papapetrou EP.  (2023) “Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia.” Blood Cancer Discovery, doi: 10.1158/2643-3230.BCD-22-0167

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Link: https://aacrjournals.org/bloodcancerdiscov/article/doi/10.1158/2643-3230.BCD-22-0167/725897/Patient-Derived-iPSCs-Faithfully-Represent-the