Furthermore, a marrow microenvironment, deficient in BPA production and, in some cases, unresponsive to IL-1 could contribute to marrow failure in some patients with AA.
In this brief article we report our experience with 2 patients with PRCA after major ABO-incompatible HSCT who were resistant to multiple therapeutic interventions and who eventually benefited from treatment with eltrombopag, a thrombopoietin mimetic approved by the US Food and Drug Administration for the treatment of patients with immune thrombocytopenic purpura or severe aplastic anemia refractory to immunosuppressive agents or not eligible for HSCT.
In vitro hemopoietic culture studies of marrow from the patient's HLA-MLC-matched siblings showed normal numbers of pluripotential and committed hemopoietic progenitors; in vitro hemopoietic colony formation from the patient was markedly subnormal, consistent with the clinical picture of severe aplastic anemia.
In this report, we describe a patient with severe aplastic anemia who developed a malignant B cell lymphoplasmacytoid proliferation 48 days after undergoing allogeneic marrow transplantation from her HLA-matched MLC-nonreactive brother.
Therefore, we concluded that the decrease of total NK cells, and CD56(bright), CD56(dim) NK cell subsets and the higher expressions of NKp46 and perforin on NK cells may cause the over-function of T lymphocytes and thus lead to hematopoiesis failure in SAA.
Next-generation-sequencing-spectratyping reveals public T-cell receptor repertoires in pediatric very severe aplastic anemia and identifies a β chain CDR3 sequence associated with hepatitis-induced pathogenesis.
First, we have tested the expression of receptor mRNAs for granulocyte-macrophage colony stimulating factor/interleukin 3 (GM-CSF/IL-3) and for c-kit protein on bone marrow (BM) cells from SAA patients.
CD34+ gene expression profiling of individual children with very severe aplastic anemia indicates a pathogenic role of integrin receptors and the proapoptotic death ligand TRAIL.
The expression of perforin, granzyme B, TNF-β and FasL in CD8+HLA-DR+ T cells was analyzed by flow cytometry and PCR, which revealed increased expression in the untreated SAA group compared with that in the control group.
We compared and analyzed HLA-A, B, C, DRB1 and DQB1 alleles in 96 Chinese severe AA (SAA) patients to those in 600 healthy people chosen randomly from the China Marrow Donor Program to investigate the association of HLA class I and II allele polymorphisms with disposition of SAA and its severity degree in Chinese population.
In conclusion, the defective Sirt1 may be correlated to the abnormal IFNγ expression in SAA patients, and activation of Sirt1 signaling may help improve the inflammatory status of SAA.
Western blotting experiments further revealed that SAA significantly increased the expression of p-Akt and p-GSK-3β, and the increase in p-GSK-3β expression was attenuated after inhibition of the Akt signaling pathway with LY294002.
Additionally, no G-CSF receptor point mutations could be seen in neutrophils, blood and bone marrow mononuclear cells from patients with cyclic or idiopathic neutropenia, and bone marrow mononuclear cells from patients suffering from severe aplastic anemia.
A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non-severe aplastic anemia, respectively.
In the candidate chromosomal region, 11p, four loci (probes) were tested, SAA (pSAA82), CALC (pHC36), HBB (Gamma-globin haplotype) and an AC repeat polymorphism at the Wilm's Tumour locus (WT1).
First, we have tested the expression of receptor mRNAs for granulocyte-macrophage colony stimulating factor/interleukin 3 (GM-CSF/IL-3) and for c-kit protein on bone marrow (BM) cells from SAA patients.