Pathology of bone marrow failure syndromes

Bone marrow failure syndromes encompass a heterogeneous group of disorders, including ‘acquired’ idiopathic aplastic anaemia and the ‘inherited’ genetic diseases of bone marrow failure, all unified by the defining feature of failure in haemopoiesis. Idiopathic aplastic anaemia is characterized by depletion in the number of haemopoietic stem cells and resulting cytopenias, associated with a classical immune signature, underlying the pathogenesis in this disease. In contrast, the genetic diseases of bone marrow failure may have non-haematological manifestations, often a prominent family history and predisposition to cancer. Although considered immune in nature, cryptic genetic mutations are increasingly being reported in idiopathic aplastic anaemia, blurring the lines of distinction between the two entities. Likewise, inherited bone marrow failure syndromes with single gene defects are also associated with secondary acquired mutations and interplay with environmental factors for disease manifestation or progression. Immunosuppressive therapy has been the cornerstone of treatment in idiopathic aplastic anaemia and underpins the dysfunctional immune response as the aetio-pathogenesis in idiopathic aplastic anaemia. Genomics is becoming crucial not only for the correct diagnosis and classification in bone marrow failure syndromes but also to screen for secondary acquired mutations which affect disease prognostication and outcomes.