Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rejection of a graft after human leukocyte antigen (HLA)-identical stem cell transplantation (SCT) can be caused by recipient's immunocompetent T lymphocytes recognizing minor histocompatibility antigens on donor stem cells. During rejection of a male stem cell graft by a female recipient, 2 male (H-Y)-specific cytotoxic T lymphocyte (CTL) clones were isolated from peripheral blood. One CTL clone recognized an HLA-A2-restricted H-Y antigen, encoded by the SMCY gene. Another CTL clone recognized an HLA-B60-restricted H-Y antigen. In this study UTY was identified as the gene coding for the HLA-B60-restricted H-Y antigen. The UTY-derived H-Y antigen was characterized as a 10-amino acid residue peptide, RESEEESVSL. Although the epitope differed by 3 amino acids from its X-homologue, UTX, only 2 polymorphisms were essential for recognition by the CTL clone HLA-B60 HY. These results illustrate that CTLs against several H-Y antigens derived from different proteins can contribute simultaneously to graft rejection after HLA-identical, sex-mismatched SCT. Moreover, RESEEESVSL-specific T cells could be isolated from a female HLA-B60+ patient with myelodysplastic syndrome who has been treated with multiple blood transfusions, but not from control healthy HLA-B60+ female donors. This may indicate that RESEEESVSL-reactive T cells are more common in sensitized patients.
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PMID:UTY gene codes for an HLA-B60-restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition. 1104 93

Regulated migration of hematopoietic stem cells is fundamental for hematopoiesis. The molecular mechanisms underlying stem cell trafficking are poorly defined. Based on a short hairpin RNA library and stromal cell-derived factor-1 (SDF-1) migration screening assay, we identified the histone 3 lysine 27 demethylase UTX (Kdm6a) as a novel regulator for hematopoietic cell migration. Using hematopoietic stem and progenitor cells from our conditional UTX knockout (KO) mice, we were able to confirm the regulatory function of UTX on cell migration. Moreover, adult female conditional UTX KO mice displayed myelodysplasia and splenic erythropoiesis, whereas UTX KO males showed no phenotype. During development, all UTX KO female and a portion of UTX KO male embryos developed a cardiac defect, cranioschisis, and died in utero. Therefore, UTY, the male homolog of UTX, can compensate for UTX in adults and partially during development. Additionally, we found that UTX knockdown in zebrafish significantly impairs SDF-1/CXCR4-dependent migration of primordial germ cells. Our data suggest that UTX is a critical regulator for stem cell migration and hematopoiesis.
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PMID:The histone demethylase UTX regulates stem cell migration and hematopoiesis. 2336 60