Glycophorin A mutations and risk of secondary leukaemia in patients treated for childhood acute lymphoblastic leukaemia

Abstract

Survivors of child acute lymphoblastic leukaemia (ALL) have a higher than expected risk of developing secondary acute myeloid leukaemia (AML). The glycophorin A (GPA) mutation assay measures the frequency of variant NO and NN erythrocytes in MN heterozygotes. A raised variant frequency (Vf) has been shown in patients treated with chemotherapy known to be at risk of secondary leukaemia. ALL patients were investigated for increased Vf using the GPA assay. Vfs at diagnosis were not significantly different from controls (NO Vf P = 0.193; NN Vf P = 0.790). During treatment Vfs increased significantly (No Vf P = 0.001; NN Vf P = 0.001). NO Vf returned to control values (P = 0.169) within 5 years from diagnosis but NN Vf remained significantly raised (P = 0.014). Three study patients developed secondary AML. At diagnosis of AML all three had significantly increased Vf. The first had a significantly raised Vf at routine follow-up 19 years following diagnosis of ALL then developed AML 3.5 years later. The second had a significantly raised NN Vf at diagnosis of ALL indicating possibly prior exposure to a mutagen or defective DNA repair involving erythroid stem cells. We conclude that a raised Vf detected by the GPA assay can act as a marker for the development of secondary induced leukaemia and can be used to screen individuals at a known high risk of this complication.