Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trisomy 8 is the most common numerical chromosomal abnormality in myelodysplastic syndromes (MDS). Paroxysmal nocturnal haemoglobinuria (PNH) is an aquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia, to MDS or to acute myeloid leukaemia. We present a patient who had trisomy 8 mosaicism at disease presentation who received therapy with all-trans-retinoic acid, responded to therapy, and developed PNH in the course of the disease. Cytogenetics at the time of PNH diagnosis showed a normal karyotype.
 ...
PMID:Trisomy 8 in a patient who responded to therapy with all-trans-retinoic acid and developed paroxysmal nocturnal haemoglobinuria. 913 54

Exposure to benzene elicits a spectrum of hematotoxicity ranging from reduction of peripheral blood cell counts to aplastic anemia and leukemia. The molecular mechanism by which benzene damages hematopoietic cells is unclear; in particular, benzene-induced aberrant gene expression has not been addressed. We analyzed differential gene expression in the peripheral white blood cells from seven female patients with occupational benzene poisoning and seven matched control subjects. In this study, we report altered expression of cytochrome P450 in the patients. All patients exhibited elevated expression of CYP4F3A encoding the leukotriene B4 (LTB(4)) omega-hydroxylase critical in the inactivation of LTB(4) in polymorphonuclear leukocytes with a -fold induction between 3 and 71. Four patients had high expression of CYP1A1, and two patients had elevated expression of CYP1B1. Expressions of CYP2B6, CYP51, and CYP27A1 were also altered in certain patients. Mechanistic analysis revealed that phenol, a major metabolite of benzene, significantly induced the expression of CYP4F3A at both mRNA and protein levels in cultured promyelocytic leukemia cells (HL-60), similarly to all-trans retinoic acid. Induction of CYP4F3 by phenol was also observed in differentiated HL-60 cells, in the proerythroid cell line K562, and ex vivo in human neutrophils. On the other hand, hydroquinone induced extensive apoptosis of the cells. The findings demonstrated, for the first time, that benzene and metabolites induce CYP4F3 in human blood cells both in vivo and in vitro. Induction of CYP4F3 may play a role in the development of benzene hematotoxicity and serve as a biomarker of benzene exposure.
 ...
PMID:Induction of CYP4F3 by benzene metabolites in human white blood cells in vivo in human promyelocytic leukemic cell lines and ex vivo in human blood neutrophils. 1902 4

Acute leukemia, secondary myelodysplasia and paroxysmal nocturnal hemoglobinuria evolving from severe aplastic anemia (AA) following immunosuppressive therapy are well recognized. However, severe AA occurring after complete remission of acute promyelocytic leukemia (APL) has been documented only once in 2009. We report a case of 30-year-old male diagnosed with APL who achieved complete cytogenetic remission with all-trans retinoic acid based induction regimen and developed severe AA few months later during maintenance therapy.
...
PMID:Severe Aplastic Anemia Manifesting After Complete Remission of Acute Promyelocytic Leukemia: Is it a Fortuitous Association? 2455 29

Severe acquired aplastic anaemia (AA) is a serious disease characterised by autoreactive T cells attacking haematopoietic stem cells, leading to marrow hypoplasia and pancytopenia. Immunosuppressive therapy combined with antithymocyte globulin and ciclosporin can rescue most patients with AA. However, the relapse after ciclosporin withdrawal and the severe side effects of long-term ciclosporin administration remain unresolved. As such, new strategies should be developed to supplement current therapeutics and treat AA. In this study, the possibility of all-trans-retinoic acid (ATRA) as an alternative AA treatment was tested by using an immune-mediated mouse model of AA. Results revealed that ATRA inhibited T-cell proliferation, activation and effector function. It also restrained the Fas/Fasl pathway, shifted Th1 towards Th2 cell development, rebalanced T-cell subsets at a relatively high level and corrected the Th1/Th2 ratio by targeting NFAT1 signalling. In addition, ATRA inhibited Th17 cell differentiation and promoted regulatory T-cell development. Therefore, ATRA was an effective agent to improve AA treatment outcomes.
 ...
PMID:All-trans-retinoic acid shifts Th1 towards Th2 cell differentiation by targeting NFAT1 signalling to ameliorate immune-mediated aplastic anaemia. 3272 37