Dr. Stuart Winter, chief research officer, is one of 52 authors on a paper that will soon be published in “Nature,” the world’s leading multidisciplinary science journal. The study is titled “The Genomic Basis of T-Lineage Acute Lymphoblastic Leukemia (T-ALL).”
The study builds upon a concept that Dr. Winter and his colleagues first started in 2001: that the use of nelarabine, an injection that interferes with the growth of cancer cells, might improve outcomes for affected patients. They also hypothesized that giving the chemotherapy drug “methotrexate” in different ways may also matter. Both of these ideas were tested by the Children’s Oncology Group (COG) in a study called AALL0434. The study accrued approximately 1,300 participants between 2007 and 2014.
As a necessary step in study enrollment, each patient’s leukemia samples were diagnosed in a single lab, and leftovers were banked for future studies; these samples were the subject of the article that will be published in “Nature.”
Over the years, Dr. Winter and his colleagues routinely met via conference calls, society gatherings, and biennial Children’s Oncology Group meetings to discuss the progress of AALL0434.
- In 2018, the team published findings that giving gradually increased doses of methotrexate worked better during the second phase of chemotherapy.
- In 2020, Dr. Winter and team published that nelarabine did, in fact, improve outcomes for those who received it.
- In 2023, Dr. Nathan Gossai, pediatric oncologist and the director of our Leukemia and Lymphoma Program, and his colleagues found that patients with leukemia in their spinal fluid who received nelarabine had so significant an improvement that nearly all of them could avoid cranial radiation as a portion of their treatment. Dr. Gossai’s work was made possible by comparing the results of AALL0434 to a later T-ALL study called COG AALL1231.
Because every patient’s leftover leukemia cells from AALL0434 were available for complex genomic analyses, Dr. Winter; Dr. David Teachey, the senior author of the Nature paper; and their colleagues were able to report the following surprising findings:
- An immature T-cell stage (when a white blood cell is inactivated) often involved changes that made the T-cells act in a cancerous way.
- Large portions of noncoding DNA, once called “junk” DNA, were involved in the gene changes that led to the cancerous behavior.
- At least 17 different pathways were involved in T-cells (white blood cells) that transformed into leukemia.
- All of these findings form the basis of a more complete understanding of how T-cells become leukemia cells.
- This study also provides insights into how new therapies might be developed to treat T-ALL in ways that we haven’t yet tested.
The study findings described in the “Nature” paper took more than two decades to complete, showing that a well-organized, large group of researchers can make important discoveries. Because of their efforts, T-ALL is slowly but surely succumbing to the relentlessness of medical research. Congratulations Dr. Winter and team on these remarkable advances!