A study led by St. Jude Children’s Research Hospital has identified a novel risk variant associated with T cell acute lymphoblastic leukemia (T-ALL). The findings appear as an advance online publication in the Journal of the National Cancer Institute. “The inherited genetics underlying this rare type of leukemia were mostly unknown prior to our study,” said senior investigator and corresponding author Jun J. Yang, Ph.D., of the St. Jude Departments of Pharmaceutical Sciences and Oncology.
“Now; we have definitively identified a gene associated with increased odds of developing T-ALL.” The researchers conducted a genome-wide association study to analyze the inherited (germline) DNA of more than 1,000 children with T-ALL as well as more than 12,000 control samples. These ALL cases are individuals treat at St. Jude and through clinical trials run by Children’s Oncology Group; the world’s largest cooperative pediatric cancer research organization.
The study identified a novel variant of the USP7 gene as playing a role in increasing the risk of developing T-ALL. This USP7 risk variant is found more often among individuals of African ancestry and may help explain why T-ALL is more common in this group. There is a genetic subtype of T-ALL characterized by over expression of TAL1.
Types of leukemia
Building upon previous research at St. Jude, Yang and his team have now shown that genetic changes in USP7; either inherited or in the DNA of the cancer cells; occur in 56% of TAL1 overexpressed T-ALL, more than any other T-ALL subtype. “These findings really confirm that T-ALL is very different from other types of leukemia; with its unique set of genetic risk factors ,” Yang said. “This work adds evidence to support the notion that USP7 plays an important role in the development of T-ALL.”
The researchers conducted additional analyses to shed light on the function of USP7 to help understand its role in the development of T-ALL. Their work shows that the inherit genetic variant is link to lower expression of USP7 and therefore some degree of reduce USP7 function. T-cell acute lymphoblastic leukaemia (T-ALL) is a type of acute leukaemia meaning that it is aggressive and progresses quickly.
Lymphoid stem cell
It affects the lymphoid-cell-producing stem cells; in paticular a type of white blood cell called T lymphocytes as opposed to acute lymphoblastic leukaemia (ALL); which commonly affects B lymphocytes. A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells);Children with ALL are often put into risk groups (such as low risk, standard risk, high risk, or very high risk); with more intensive treatment given to higher risk patients.
Generally, children at low risk have a better outlook than those at very high risk. But it’s important to know that even children in higher risk groups can often still be cured.Children with early B-cell ALL subtypes generally do better than those with mature B-cell (Burkitt) leukemia. The outlook for T-cell ALL seems to be about the same as that for B-cell ALL as long as treatment is intense enough.