Genetic testing for the enzyme thymidylate synthase could identify patients who are more likely to have a poor outcome if they are diagnosed with acute lymphoblastic leukaemia.
Thymidylate synthase is an essential enzyme in proliferating cells, and an important target for various cancer chemotherapies, including methotrexate glutamates. Inhibition of this enzyme results in deoxythymidine triphosphate depletion, and subsequently in chromosome breaks and cell death.
Dr Maja Krajinovic and colleagues at the Département de Pédiatrie, Université de Montréal, Montréal, Canada, investigated outcome in 205 children being treated with methotrexate for acute lymphoblastic leukaemia. They looked for the possible association between a variant of the gene coding for thymidylate synthase, in which a specific triple repeat alteration is associated with increased expression of thymidylate synthase.
The DNA samples from the children of buccal epithelial cells, peripheral blood, or bone marrow in remission, were analysed for variation by polymerase chain reaction amplification.
The clinicians found that children who were homozygous for the triple repeat were four times more likely to have a poorer outcome than children with other genotypes. Risk remained unchanged after inclusion of known clinical prognostic factors, such as sex, age, WBC count, cell type, DNA index and treatment protocol.
תגובות רוצה להצטרף לדיון?
יש להתחבר כדי להגיב.
התחבראין תגובות עדיין. היה הראשון להגיב!