PG-AML is a genomic analysis research program designed to personalize treatment for children with myeloid leukemia.
Acute Myeloid Leukemia in Children
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. AML is the second most common leukemia in children after acute lymphoblastic leukemia (ALL). Approximately 80 children in France are diagnosed with AML each year. It is most common during the first two years of life and during adolescence.
Although more than 90% of children achieve complete remission, the relapse rate in the first complete remission remains high (40-50%) despite advances in understanding tumor mechanisms, risk group stratification, and progress in intensive chemotherapy and bone marrow transplantation. The overall risk of relapse remains the most common cause of death.
About PG-AML
Improvements in the treatment of acute lymphoblastic leukemia (ALL) in children are due to the development of extremely sensitive genomic technologies to monitor the response to treatments. These technologies allow the detection of one leukemic cell among 100,000 normal cells. The incredible sensitivity of these technologies to detect MRD (measurable or minimal residual disease) has enabled personalized adjustment of therapy. Thus, a child with an excellent response to therapy, manifested by very low or negative MRD, requires less toxic chemotherapy to be cured. A similar child whose response to initial therapy is poor, manifested by high MRD, will require intensive chemotherapy, possibly with the addition of a bone marrow transplant.
One of the major challenges of pediatric acute myeloid leukemia (AML) is the lack of highly sensitive methodologies to detect the disease’s response to therapy through genomic approaches similar to those used to treat ALL. We propose a new genomics-based methodology to overcome this challenge. We will use this new approach not only to determine the response to therapy but also to characterize leukemic cells that remain resistant to therapy. This could lead to the identification of new drugs that could overcome this resistance.
This research project is based on a collaboration between two researchers with complementary skills. Prof. Yosef Maruvka is an internationally renowned expert in computational genomics, and Prof. Shai Izraeli is a well-known physician-scientist in the field of pediatric leukemia. This project will leverage a large pediatric AML database from clinical trials that exists in Prof. Izraeli’s department. As co-chair of the ITCC leukemia committee, the methodologies developed in this project will be quickly translated and disseminated among the international leukemia community as crucial tools to determine the effectiveness of new AML drugs. The existence of such genomic tools will allow precise adjustment of therapies for each child with AML.
Project Progress
The study initially started with a preliminary approach to validate the overall protocol. Thus, using samples taken from 4 patients, they were able to perform comprehensive sequencing. Between 80 and 250 mutations per patient were identified.
This project aligns with the one led by Dr. Hirsch, funded by the 2024 Rallyes du Cœur, which proposes to refine the analysis of MRD using next-generation sequencing approaches.
Summary of the PG-AML Project
- Lead Investigators: Prof. Shai Izraeli
- Program Duration: January 2023 – January 2025
- Countries Involved: Israel
- Funding by Fight Kids Cancer: €500,000, including funding by Imagine for Margo: €283,380
