LLSC 2022

Childhood Blood Cancer Research Innovation Grant

In 2022, Kindred Foundation partnered with The Leukemia and Lymphoma Society of Canada to co-fund two childhood blood cancer research innovation grants.  We are proud to announce the two projects that we co-funded:

Dr. Cynthia Guidos | SickKids, Toronto 

Identifying the Genetic Changes that Lead to Ruxolitinib Resistance 

Modern chemotherapy regimens can cure acute lymphoblastic leukemia (ALL) in most children, adolescents, and young adults. Unfortunately, outcomes remain poor for children whose ALL is caused by certain high-risk genetic mutations, known as Ph-like ALL. This subtype occurs very commonly in children and is more frequent in individuals of Hispanic/Latino and Indigenous ancestry. Ph-like ALL often comes back even with the best available chemotherapy.  

A new targeted therapy called ruxolitinib was created to block an important pathway that contributes to the cancerous behaviour of Ph-like ALL cells. A phase 2 clinical trial is ongoing to test whether adding ruxolitinib to chemotherapy can decrease relapses in children with Ph-like ALL. However, some children have already relapsed, suggesting that their leukemia cells found a way to outsmart the drugs and become resistant.  

In this project, the researchers are studying blood and bone marrow samples from pediatric Ph-like ALL participants in the clinical trial. They hope to learn why leukemia cells can sometimes outsmart the drugs and lead to relapse, either by developing DNA mutations or rewiring the pathways inside the cells to hide from the drugs. The results will be used to identify new therapies that attack other leukemia cell targets with a goal of overcoming or even preventing resistance to ruxolitinib in patients with Ph-like ALL. 

2025 UPDATE: A newer targeted drug, ruxolitinib, was designed to block a key pathway involved in this disease, and a recent Children’s Oncology Group clinical trial tested whether adding it to chemotherapy could reduce relapse. By closely studying leukemia cells from children in this trial, we found that different genetic changes are linked to distinct cell behaviours at diagnosis, and that leukemia cells can change over time during treatment. These findings may help guide more personalized treatment approaches and support the development of new therapies to prevent or overcome drug resistance in children with Ph-like ALL.

Dr. Florian Kuchenbauer | BC Cancer, Vancouver  

MiR-193a-Based LNP Drug Treatment for Pediatric Acute Myeloid Leukemia 

Acute myeloid leukemia (AML) is a blood cancer with poor outcomes. Currently, treatment still relies on chemotherapies, which have an impact on the physical and mental development of children.  

COVID-19 and mRNA-based therapeutics used to treat it have changed the world. Key to their success was the

encapsulation of mRNAs within liposomal nanoparticles (LNPs).  

Dr. Kuchenbauer’s research group and others have recently highlighted the potential of microRNA (miRNA) encapsulated LNPs to target specific mutations in leukemias, with fewer side effects. The team’s previous data showed that miR-193a (a gene associated with cancer) is significantly decreased in pediatric normal karyotype AML (CN-AML) . In CN-AML, it has been shown that engineered over-expression of miR-193a slowed down the development of AML.  

An LNP-miR-193a-3p-based drug (INT-1B3) is currently being studied in a clinical trial for solid tumours and the researchers will be testing this drug in pediatric CN-AML models. They aim to pioneer novel LNP-miRNA-based formulations for the treatment of pediatric AML. This innovative approach will help to reduce the chemotherapy burden on children, improve treatment outcomes, and help to foster normal development in a frail and underserved population.

2024 UPDATE: Understanding how cancer develops and progresses could lead to finding treatments that identify what “switches” need to be turned on and off to suppress tumour growth.  Dr. Kuchenbauer and his team looked at a specific gene mutation (WT1) in AML and the role of a small molecule (MiR-193a) to understand its tumour-suppressing potential.  Their work also showed some promise in using a form of MiR-193a (a liposomal nanoparticle), which slowed the growth of AML in laboratory models.  They made key discoveries about WT1 and miR-193a, have motivated additional scientific work on using liposomal nanoparticles to deliver (RNA-based) therapies, and are collaborating on new delivery methods to develop targeted therapies for AML patients.