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What causes aplastic anaemia?

Journal Title: 
Leukemia
Primary Author: 
Gale RP
Author(s): 
Gale RP, Hinterberger W, Young NS, Gennery AR, Dvorak CC, Hebert KM, Heim M, Broglie L, Eapen M
Original Publication Date: 
Thursday, April 27, 2023
Bone Marrow Disease(s): 

Aplastic anaemia has diverse aetiologies including: (1) direct damage to haematopoietic stem or progenitor cells such as from chemicals, drugs and ionising radiations; (2) an abnormal bone marrow micro-environment, (3) immune-mediated mechanism(s); or (4) combination of these. Aetiologies may differ between persons with similar phenotypes and even genotypes [1] (References in the Supplementary). These aetiologies are not mutually exclusive and can be tested, in part, by analysing results of haematopoietic cell transplants between genetically identical twins, one of whom has aplastic anaemia. Recovery of bone marrow function after transplanting haematopoietic cells from a twin without pretransplant conditioning favours damage to haematopoietic stem or progenitor cells as the aetiology and suggests that a bone marrow micro-environment abnormality is an unlikely aetiology. It also likely excludes a congenital abnormality as aetiology because the donor twin has normal bone marrow function. In contrast, failure to recover after the first unsuccessful transplant without pretransplant conditioning, but recovery after the second transplant with it sometimes combined with posttransplant immune suppression, favours an immune aetiology.