Unique new models will empower leukaemia research


Tisch Cancer Center scientists have developed unique models of acute myeloid leukaemia (AML), creating a transformative resource to study this cancer and eventually its drug response and drug resistance.

The research was presented at the annual meeting of the American Association of Cancer Research and simultaneously published in Blood Cancer Discovery, a journal of the American Association for Cancer Research.

This discovery is the first time that powerful models have been created that are nearly identical to AML found in patients. The researchers said that these models represent the disease accurately in genetic composition and in disease characteristics found in laboratory cell cultures, animal models and patients.

AML has only a 29% survival rate, and is a fast-growing cancer. It’s often widespread in the bone marrow and the blood when it’s first discovered in a patient, so being able to study the cancer, its progression and its response to drugs in accurate and viable cell lines is crucial.

“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,” said senior author Eirini Papapetrou, Professor of Oncological Sciences and Medicine, Hematology and Medical Oncology at The Tisch Cancer Institute, a part of the Tisch Cancer Center, and Director of the Center for Advancement of Blood Cancer Therapies (CABCT) at the Institute of Regenerative Medicine at Mount Sinai.

“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.”

Genetic reprogramming technology

To create these models, researchers used genetic reprogramming technology to convert blood or bone marrow cells from 15 patients representing all major genetic groups of AML to a particular type of stem cells (called induced pluripotent stem cells) that can mimic different stages of disease progression.

Importantly, the leukaemia cells derived from these lines can be transplanted into animal models and create a remarkably similar disease as in the patients.

Many of these lines have been distributed to other researchers, who, along with Dr Papapetrou and her colleagues, will pursue several new studies into leukaemia pathogenesis and drug responses.

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