Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia.
نویسندگان
چکیده
Treatment of severe aplastic anemia with antithymocyte globulin (ATG) and cyclosporin leads to clinical remission in a large proportion of patients. As many as 10% to 57% of these patients, however, develop paroxysmal nocturnal hemoglobinuria (PNH). We and others have observed that this secondary PNH appears to be more indolent than classical PNH, which results from an acquired mutation in the PIG-A gene. In the present study, we compared PIG-A mRNA transcripts in affected cells from patients with secondary PNH and patients with classical PNH. All four of our aplastic patients who developed PNH had a negative Ham test at diagnosis. Two of the four showed a positive Ham test within 3 months after ATG/cyclosporin administration, one developed a positive test at 6 months, and another at 18 months after immunosuppressive therapy. All four patients remain transfusion-independent with no thrombotic episodes after a mean follow-up of 30 months (range, 6 to 63 months). Reverse transcription-polymerase chain reaction (RT-PCR) of PIG-A transcripts in DAF-/CD59- neutrophils or lymphocyte lines of the four patients showed PIG-A abnormalities in all cases. Transition of C163 to T was found in one, a 14-bp deletion (positions 1141 to 1154) was found in the second, deletion of C39 was found in the third, and two mutations, transition of C55 to T and transversion of T762 to A, were found in the fourth. These abnormalities compared with findings of abnormal RNA splicing causing a 133-bp deletion, a 4-bp insertion (between positions 578 and 579), loss of A767, and loss of C575 in four patients with primary PNH. We conclude that secondary PNH that evolves out of aplastic anemia, like classical PNH, is associated with mutations in the PIG-A gene. The apparent indolent nature of this disease probably reflects early detection.
منابع مشابه
Paroxysmal Nocturnal Hemoglobinuria Presenting with a Left Intraventricular Thrombus in a Patient with Prior Thymoma and Aplastic Anemia
We report the case of a 37-year old man presenting with a left ventricular cardiac thrombus in the setting of subclinical paroxysmal nocturnal hemoglobinura (PNH) developing two years after immunosuppressive therapy for thymoma-associated aplastic anemia. The literature regarding the interplay between autoimmunity and immunosuppression, aplastic anemia, thymoma and the emergence of PNH is revie...
متن کاملParoxysmal nocturnal hemoglobinuria clone in 103 Brazilian patients: diagnosis and classification
BACKGROUND Paroxysmal nocturnal hemoglobinuria is an acquired chronic hemolytic anemia, which often manifests as peripheral blood cytopenias and thrombosis. OBJECTIVE The aim of this study is to describe a Brazilian population of paroxysmal nocturnal hemoglobinuria patients. METHODS One hundred and three paroxysmal nocturnal hemoglobinuria cases were retrospectively reviewed and the clinica...
متن کاملParoxysmal nocturnal hemoglobinuria with acute leukemia.
T HE OCCURENCE of impaired marrow function in paroxysmal nocturnal hemoglobinuria (PNH) has long been recognized. A smaller group of patients, with an initial diagnosis of aplastic anemia, have been noted to develop signs of PNH during the course of their illness.1 Such persons have been said to have “the aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.”2 Also evident, in some case...
متن کاملParoxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine.
BACKGROUND Clones of glycosylphosphatidylinositol-anchor protein-deficient cells are characteristic in paroxysmal nocturnal hemoglobinuria and are present in about 40-50% of patients with severe aplastic anemia. Flow cytometry has allowed for sensitive and precise measurement of glycosylphosphatidylinositol-anchor protein-deficient red blood cells and neutrophils in severe aplastic anemia. DE...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 86 12 شماره
صفحات -
تاریخ انتشار 1995