Discovery of a second, distinct development pattern of leukemic conversion from paroxysmal nocturnal hemoglobinuria.

Abstract

The incidence of leukemic conversion during the clinical course of paroxysmal nocturnal hemoglobinuria (PNH) has been reported to be 0.6-2.9%. Such an association is logically linked to the progression of PNH to acute leukemia, especially the M6 subtype of acute myeloid leukemia (AML-M6). In many of these cases (11/26, 42%), leukemic conversion from PNH is associated with development of AML-M6. A literature review including our cases showed that this leukemic conversion from PNH has two distinct development patterns. In type 1, leukemic clones were derived from non-PNH clones in most cases, and the PNH phenotype of erythrocytes disappeared with progression. In one of our cases, however, the patient was diagnosed with concomitant PNH and AML-M6, and leukemic cells were observed alongside CD55-negative and CD59-negative PNH clones. In Type 2 cases such as this one, conversion of PNH is characterized by the coexistence of leukemic cells with PNH clones. Flow cytometry revealed that CD34-positive blast cells were deficient in CD55 and CD59. In Type 2, PNH clones do progress into malignancies, albeit rarely, demonstrating a distinct second development pattern of leukemic conversion from PNH.