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Research Highlight | October 16, 2019

Toronto-based team identifies potential target to supress leukemia stem cells

A team of TFRI-funded scientists led by Dr. John Dick (Princess Margaret Cancer Centre) has discovered a new target that, when exploited, may be able supress leukemia stem cells (LSCs), stopping the disease in its tracks or preventing relapse in patients who have already undergone treatment.

As described in a paper published in Blood (May 2019), the team used a novel approach to screening that allowed them to identify that INKA1, a gene that had never been studied before in the context of cancer, played an important roll in stem cell persistence in acute myeloid leukemia (AML), a form of the disease which is often characterized with post-therapy recurrence.

“We set out to uncover molecular mechanisms underlying LSC persistence irrespective of the patient-specific mutational landscape to identify novel druggable targets applicable to a wider cohort of leukemia patients,” explains first author Dr. Kerstin Kaufmann. “With our study we highlight not only the feasibility of this approach but also provide a novel target for therapeutic approaches aiming either at LSC eradication or suppression to avoid disease relapse.”

Leukemia stem cells are understood to be the source from which leukemia arises. In recent years, a growing body of evidence has shown that the molecular properties of these cells are associated with clinical outcomes in patients. Therefore, understanding the characteristics of these cells is paramount to understanding why leukemias form or become resistant to treatment, while also providing insights into how these cells can be eliminated.

In this context, the team’s discovery of INKA1 as a regulator of stem cell persistence could be a game-changer, opening the door to the creation of treatments that attack specific vulnerabilities in cancer stem cells in leukemia and other cancers.

“This work sets the stage for future investigation of the roles of activation and latency in maintenance of LSC function and therapy resistance,” says Dr. Kaufmann. “Identifying and dissecting such programs will potentially define new strategies for targeting LSC vulnerabilities in AML.”

Study

A stemness screen reveals C3orf54/INKA1 as a promoter of human leukemia stem cell latency

Authors

Kerstin B. Kaufmann,  Laura Garcia-Prat, Qiang Liu, Stanley W. K. Ng, Shin-Ichiro Takayanagi, Amanda Mitchell, Erno Wienholds, Peter van Galen, Christian A. Cumbaa, Mike J. Tsay, Chiara Pastrello, Elvin Wagenblast, Gabriela Krivdova, Mark D. Minden, Eric R. Lechman, Sasan Zandi, Igor Jurisica, Jean C. Y. Wang, Stephanie Z. Xie, and John E. Dick

Funding

This study was partially funded by a Terry Fox New Frontier Program Project Grant in Development of Stemness-Based Prognostic Biomarkers and Therapeutic Targets