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A recent study by Hira et al. [20] found accelerated bone marrow failure in FA patient carriers of dominant-negative ALDH2 alleles, confirming the adverse effects of ethanol metabolism in the absence of a functioning FA pathway.
Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly larger amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared with young cells, and bone marrow failure in animals devoid of DNA repair factors.
These results suggest that partially impaired telomerase activity arising from a haploinsufficiency might induce bone marrow failure in humans.
X-linked dyskeratosis congenital (X-linked DC), marked by skin and bone marrow failure in humans, is caused by point mutations in the gene encoding the nucleolar protein dyskerin.
We found high rates of significant bone marrow failure in treatment-refractory patients.
The novel germline T1129P mutation in the TERT gene identified in a consanguineous Libyan family leads to DKC with progressive bone marrow failure in all homo-zygous individuals.
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The same hypothesis could be evoked for all FA patients presenting with a mild clinical phenotype or who develop bone marrow failure later in life, as proposed in a recently published study (61).
Common clinical findings in immunocompromised patients are fatigue, hepatitis, enterocolitis, encephalitis, pneumonitis, bone marrow failure and in AIDS patients also retinitis [ 16].
Acute leukaemias tend to have quite a sudden onset, usually over a few weeks, with symptoms of bone marrow failure resulting in infection, bruising and tiredness or dyspnoea on account of anaemia.
While the stem cell is at the heart of the disease, and certainly responsible for the bone marrow failure seen in DC, some of the non-haematological features and those of premature aging might also be explained by other means.
The bone marrow failure resulted in decreased production of functional RBCs and coupled with cancer related inflammatory response [ 18] and/or chemotherapy induced [ 19, 20] increase in destruction of RBCs; blood loss leads to decrease in HGB, RBC count, and HCT.
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