title: Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.
abstract: We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. 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, showing 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 performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan. dtanaka@hiroshima-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Imamura
authors.forename: N
authors.initials: N
authors.lastname: Oguma
authors.forename: T
authors.initials: T
authors.lastname: Shintani
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Hyodo
authors.forename: K
authors.initials: K
authors.lastname: Oda
authors.forename: A
authors.initials: A
authors.lastname: Kimura
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000741:Anemia, Aplastic / Q000150:complications / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D018957:CD59 Antigens / Q000032:analysis; D020732:Cytogenetic Analysis; D005260:Female; D016368:Frameshift Mutation; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018957:CD59 Antigens; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein