Lauren Dempsey, MS in Biomedicine and Law, RN, FISM News
Scientists from multiple scientific institutions have published new research that brings doctors one step closer to understanding infant leukemia.
While cancer treatments have improved in older children with leukemia, infants continue to have very poor outcomes. A team of researchers from Wellcome Sanger Institute, Great Ormond Street Hospital, and Newcastle University, though, have discovered small differences in cells that cause B acute lymphoblastic leukemia (B-ALL) that may help to explain why some cases of infant cancer are more severe.
Researchers evaluated 1,665 mRNA molecules which were representative of childhood acute lymphoblastic leukemia (ALL) and acute myelocytic leukemia (AML). Both types of leukemia are cancers of the blood, however with ALL the bone marrow makes too many lymphocytes and with AML the bone marrow makes too many myeloblasts. Lymphocytes and myeloblasts are both white blood cells.
One theory that scientists have about infant and childhood leukemia is that it develops before birth. Researchers used hematopoietic stem cells as a reference point. These cells are produced within the bone marrow and are the cells that produce red blood cells, white blood cells, and platelets. Cancer occurs when there is a mutation while the stem cells are developing into mature cells.
Dr. Jack Bartram from Great Ormond Street Hospital and co-author of the study explained that researchers may have uncovered why some children are more responsive to treatment than others. He said that the research showed that the difference is due to a specific genetic mutation.
Cancers with more ‘mature’ early lymphocyte precursors have characteristics that seem to respond better to treatment. These more mature cells are more common in B-ALL in older children but sadly not for our younger patients, meaning the treatment is less effective. The challenge now is to develop our understanding and confirm these suspicions so that we can improve treatments for all patients.”
The researchers focused on infant B acute lymphoblastic leukemia (B-ALL) cases that were caused by changes to the KMT2A gene. They were able to compare cancer cells to normal blood cells and found that there were significant cell changes. With this form of leukemia, the disease develops from B lymphocytes or B cells. B-ALL was once universally fatal, but with current therapeutics it is now curable in most childhood cases.
The exception is in cases of B-ALL in children aged 1 year or younger. In these children the success rate of treatment is about 50%, and this rate has not improved over the last twenty years. It is estimated that 70-80% of infant B-ALL cases are associated with a mutation of the KMT2A gene which may be related to poor outcomes. Infant B-ALL is currently treated with chemotherapy, as bone marrow transplants have been found to be ineffective.
Dr. Sam Bebiati from the Wellcome Sanger Institute and co-author of the study said “Though it is too early to draw definitive conclusions about why B acute lymphoblastic leukemia has much poorer outcomes in infants than in older children, this study offers compelling evidence that the maturity of the cells involved is a key factor. As well as generating new drug targets, these data will allow us to observe how the ‘cell type’ of certain cancers corresponds to patient outcomes, allowing us to better assess disease severity and determine the best course of treatment.”
The research will help to provide better understanding of the gene mutation that contributes to B-ALL. This will lead to the development of new treatment options for infant leukemia, and hopefully lead to the saving of thousands of lives.