Diagnostic problems in acquired bone marrow failure syndromes.

Abstract

The dysplastic signs in PNH patients can be ascribed to co-existing MDS clones, which over time can give rise to acute myeloid leukemia. Abnormal HSPC clones may be present and exhibit dysplastic signs at the diagnosis of BM failure-type PNH or subclinical PNH (PNHsc). However, PNH-phenotype cells are rarely detected in patients in bona fide preleukemic states, such as RARS and RAEB [2]. A recent genomic analysis of hemolytic PNH patients revealed a low incidence of genomic abnormalities associated with MDS [3]. A genomic analysis of a large number of AA patients recently published by our group revealed a lower frequency of abnormalities in MDS-related genes, such as TP53 and RUNX1, in AA patients with PIGA mutations than in patients without PIGA mutations [4]. It is thus unlikely that the dysplastic signs in PNH patients represent co-existing abnormal MDS clones. Dysplastic signs in immature blood cells can be caused by extrinsic factors, such as nutritional deficiencies and toxins. Some patients with collagen diseases show dysplastic signs of immature cells similar to those of patients with MDS. In patients with AA characterized by small populations of PNH-type cells, dysplastic features typically disappear after they achieve hematologic remission following immunosuppressive therapy [5]. Reversible dysplasia, such as occurs in inflammatory diseases and immune-mediated BM failure, suggests that inflammatory cytokines produced locally in the BM may induce dysplastic changes in immature blood cells. It is thus important to bear in mind that the immune pathophysiology of BM failure, which allows PIGA-mutant HSPCs to contribute to hematopoiesis, is often associated with some degree of erythroid and granulocytic dysplasia. Introduction