Clinical evidence for a link between
aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and hypoplastic leukaemia is provided by studies of clonal disorders, which may be a complication of congenital or acquired
aplastic anaemia. Fanconi's anaemia is the most common
congenital disorder and leukaemia occurs in at least 10% of cases. In acquired
aplastic anaemia, a high incidence of
myelodysplastic syndrome (MDS) was noted in patients with
aplastic anaemia, seemingly cured of their aplasia by
antilymphocyte globulins (ALG). In a recent survey, the 10-year cumulative incidence rates were 9.6% for MDS, 6.6% for acute leukaemia (115-fold higher than in the general population).
Biological evidence is provided by bone marrow morphology, as a certain degree of dysmyelopoiesis is not unusual in
aplastic anaemia. Cytogenetic analyses in
aplastic anaemia are scarce, but data have shown clonal
cytogenetic abnormalities at diagnosis in otherwise typical
aplastic anaemia. Recently, flow cytometry to assess the
glycosyl-phosphatidylinositol (GPI) molecule defect in PNH has demonstrated that a significant proportion of patients with otherwise typical
aplastic anaemia have, in fact, a GPI defect due to alterations within the PIG-A gene. Finally,
aplastic anaemia patients were recently reported to have molecular evidence of clonal haematopoiesis; this must now be discussed in light of recent clonality studies in normal individuals. The clinical and
biological evidence for a link between
aplastic anaemia, PNH and hypoplastic leukaemia allows the generation of a model of
aplastic anaemia as a possible pre-pre-leukaemic disorder.