Acute myeloid leukemia (AML) is an aggressive cancer of the blood system. Despite advances in AML treatment, only 21% of patients survive >5 years. If an  allogeneic stem cell transplant (allo-HSCT) can be performed, the 5-year survival becomes 30-50%. One reason why this treatment is effective is because of the role of donor immune cells that fight leukemia in a process known as graft-versus-leukemia effect. Despite this treatment’s effectiveness, for reasons not well understood, many patients relapse. In these patients, AML returns aggressively and is associated with shorter survival. Continued relapse susceptibility limits the outcome of allo-HSCT in AML.

The LSD1 enzyme (protein) is a promising new target for treating AML. Blocking this enzyme can change the way malignant blood cells behave, remove malignant stem cells, and even activate an immune response against malignant cells. Bomedemstat, a drug that blocks LSD1’s functions in the cell, is well tolerated and in early clinical  studies is effective in different blood disorders but has yet to be tested in its ability to target AML in a combination treatment. We will use Bomedemstat and test in pre-clinical models our hypothesis that it can prevent relapse after allo-HSCT. We will also study the features in leukemia that may be used as biomarkers and may allow us to identify patient groups who will benefit from this approach. With early clinical data available on Bomedemstat in other settings, the results of our study will enable a clinical phase 1/2 trial as maintenance strategy after allo-HSCT.

Funding Agency: Ontario Institute for Cancer Research
Collaborators: Imago Biosciences Inc.

Acute Myeloid Leukemia (AML) is a type of blood cancer that is a major cause of death and suffering in Canadian patients. Chemotherapy and bone marrow (BM) transplantation can cure the disease in some patients, but relapse of AML is common and unfortunately resists chemotherapy upon return. The goal of our research program is to understand what determines the different responses of AML to treatments by patients. To understand the response better, we are studying very rare AML cells (1 in 100,000) that remain in the patient’s BM after treatment and this is called measurable residual disease (MRD). The goal of the program is to study human patient AML samples collected over the course of treatment to see how AML cancer cells react to treatment over time, and to see what, if any, AML cells are left behind after chemotherapy. The critical infrastructure for the safe storage for this valuable material is contained within this CFI-funded Research Cancer Stem Cell Bank. This bank consists of the cryogeneic storage system essential for maintaining viable samples for study. We are further testing how the cells grow in a petri dish and in immunocompromised animals, which allows us to test the effect of novel treatments on the primary AML samples. The necessary equipment in this novel tissue culture lab is part of our Functional Stem and Progenitor Assessment Unit. The most important of the infrastructure is the Single Cell Molecular Characterization Unit, which allows to detect rare AML cells after treatment and that allows to determine in individual cells which genes are currently active. The infrastructure in these units is contributing to our understanding of AML relapse and will lead to a better new understanding of how cancer returns after therapy and possibilities to intervene and prevent relapse. The equipment is an integral part of McMaster’s new Centre for Discovery in Cancer Research.

Funding Agency: Canadian Foundation for Innovation and Ontario Research Fund – Research Infrastructure

The research program is studying the impact of epigenetic interventions on cellular mechanisms in myeloid leukemia cells such as differentiation, metabolism, or immune activation.

Using state-of-the-art model systems, the lab is investigating how treatment with epigenetically active agents alters metabolic processes.

Funding Agency: Marta and Owen Boris Foundation

Collaborators: Structural Genomics Consortium; Imago Biosciences Inc.