Leukemia arising out of paroxysmal nocturnal hemoglobinuria

In paroxysmal nocturnal hemoglobinuria (PNH), one or more hematopoietic ste m cells that are defective in GPI anchor assembly as a result of mutation i n the PIG-A gene preferentially expand in the bone marrow and give rise to peripheral blood elements that are deficient in GPI anchored protein expres sion. According to current concepts, 5-15% of PNH patients develop leukocyt e dyscrasias which invariably are acute myelogenous leukemia (AML). In this review, the literature from 1962 to the present is analyzed regarding the type of leukocyte dyscrasia, incidence, and cytogenetic features of the abn ormal cells that have been reported. Among a total of 119 cases that are we ll-documented, 104 myeloid dyscrasias involving several categories in addit ion to AML, as well as 15 lymphoid dyscrasias are described. Of 1,760 patie nts in 15 series that contain 20 or more patients, 16 (1%) are reported as having developed "acute leukemia." However, of 288 listed as having died, 1 3 (5%) are recorded as having had "acute leukemia." In 32 of the patients w ith hematological dyscrasias where karyotypes were analyzed, 7 were found t o be normal and 25 found to harbor various alterations with the +8 abnormal ity present in 8. In 5 of 7 instances evidence indicates that the dyscratic cell arises from the PNH clone, Processes potentially involved in the evol ution of the dyscratic cells from PNH clones are discussed.