Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome

We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglob inuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacke d CD59 antigen on their surface and were positive for P-glycoprotein. Heter oduplex and single-strand conformation polymorphism analysis followed by se quencing of the leukemic cells in the bone marrow disclosed 1 frameshift-ty pe mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) ge ne, which deductively produces truncated PIG-A protein. These findings prov ide direct evidence that the leukemic cells evolved from the affected PNH c lone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH. AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, sh owing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was per formed successfully with recovery of CD59 antigen on bone marrow hematopoie tic cells: however, leukemia relapsed 4 months after PBSCT. Leukemia derive d from PNH may be resistant to intensive chemotherapy, and a highly myeloab lative regimen may be required for stem cell transplantation to eradicate t he PNH-derived leukemia clone. (C) 2001 The Japanese Society of Hematology.