Immunologic effects on the haematopoietic stem cell in marrow failure

Abstract

Acquired bone marrow failure (BMF) syndromes comprise a diverse group of diseases with variable clinical manifestations but overlapping features of immune activation, resulting in haematopoietic stem and progenitor cells (HSPC) damage and destruction. This review focuses on clinical presentation, pathophysiology, and treatment of four BMF: acquired aplastic anaemia, large granular lymphocytic leukaemia, paroxysmal nocturnal haemoglobinuria, and hypoplastic myelodysplastic syndrome. Autoantigens are speculated to be the inciting event that result in immune activation in all of these diseases, but specific pathogenic antigens have not been identified. Oligoclonal cytotoxic T cell expansion and an active role of proinflammatory cytokines, primarily interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), are two main contributors to HSPC growth inhibition and apoptosis in BMF. Emerging evidence also suggests involvement of the innate immune system.

Keywords: Aplastic anaemia; Bone marrow failure syndromes; Hypoplastic myelodysplastic syndrome; Large granular lymphocytic leukaemia; Paroxysmal nocturnal haemoglobinuria.