CURE2MILL is a research program aimed at improving the treatment of children affected by the most severe forms of acute lymphoblastic leukemia.
About Childhood Leukemias
Childhood leukemia is similar to adult leukemia but can present certain differences. Acute leukemia is a type of cancer characterized by the spread of cancerous cells originating from the bone marrow stem cells. These cells multiply chaotically, invade the bone marrow, enter the bloodstream, and can thereby infiltrate the entire body. This proliferation disrupts the production of all blood cells (white and red blood cells, platelets). In 2023, it is the most common cancer in children, accounting for approximately 30% of pediatric cancer cases.
The two main types in children are acute lymphoblastic leukemia (80% of cases) and acute myeloid leukemia. The exact causes of leukemia in children are not always clearly defined, but it is believed to be associated with genetic, environmental factors, or a combination of events occurring at the level of bone marrow stem cells.
About Cure2MILL
Significant advances in treating the most common form of childhood blood cancer, acute lymphoblastic leukemia (ALL), continue to be among the greatest achievements in pediatric oncology. While only 1 in 10 children diagnosed with ALL survived in the 1960s, nowadays, 9 out of 10 children survive. Thus, pediatric ALL can be considered a curable disease. Unfortunately, this is not true for all patients diagnosed with ALL, especially infants. Most babies diagnosed with ALL carry a specific mutation in the MLL gene. This anomaly makes ALL in infants very aggressive and challenging to treat. Consequently, about half of these infants will relapse, and only 3 to 4 out of 10 babies can be completely cured of ALL. This underscores that currently available treatments are clearly inadequate to cure ALL in infants with an MLL mutation, and more effective treatment options must urgently be developed.
To rapidly identify more effective therapeutic strategies, this project is led by an international collaborative research team. By combining the expertise of research groups in the UK, Italy, Spain, and the Netherlands, all with extensive experience in pediatric acute leukemia, the chances of quickly finding treatments for all infants affected by ALL are greatly enhanced. Moreover, the team will operate under the auspices of the INTERFANT and UKALL treatment consortia, which internationally coordinate the treatment of ALL in infants with an MLL mutation.
Thus, the team has access to a relatively large cohort of patient samples for this project. With the aid of smart and clinically relevant laboratory models, researchers in this project aim to:
- Understand the mechanisms that make infant ALL aggressive
- Identify new treatment options by targeting these mechanisms
- Provide evidence that these newly identified treatments will potentially work very well when applied to actual patients.
Once these steps are accomplished, the results will be discussed with the INTERFANT/UKALL consortium to provide better risk stratification and transition of identified treatments into an international clinical setting. This will enable infants with ALL to receive more personalized, effective, and less aggressive treatments.
Project Progress
The team has identified a gene responsible (NG2) for the resistance of infant ALL to corticosteroids, the main treatment given to them. Additionally, pharmacological products capable of blocking this gene have been identified, enhancing the effect of glucocorticoids more significantly in vitro. These promising initial results need confirmation through in vivo studies, and researchers are also exploring new molecules. Finally, the team is investigating the role of another gene, Musashi-2, in infant ALL, opening new avenues for promising research.
Summary of the Cure2MILL Project
- Lead Investigators: Dr. Ronald W. Stam
- Program Duration: January 2023 – January 2025
- Countries Involved: Netherlands, Spain, UK, Italy
- Fight Kids Cancer Funding: €492,000, including Imagine for Margo funding: €278,846
