نتایج جستجو برای: raralpha
تعداد نتایج: 280 فیلتر نتایج به سال:
Acute promyelocytic leukemia (APL) is always associated with chromosomal translocations that disrupt the retinoic acid receptor alpha (RARalpha) gene. Whether these translocations relate to a role for endogenous RARalpha in normal granulopoiesis remains uncertain because most studies addressing this question have used non-physiological overexpression systems. Granulocyte differentiation in cell...
Expression of a bcr-3 isoform of retinoic acid receptor alpha-promyelocytic leukemia (RARalpha-PML) in mice expressing a bcr-1 isoform of PML-RARalpha is associated with increased penetrance of murine acute promyelocytic leukemia (APL) and the frequent acquisition of an interstitial deletion of one copy of mouse chromosome 2 (del(2)). To determine whether the isoform of RARalpha-PML is importan...
PML/RARalpha is the abnormal protein product generated by the acute promyelocytic leukemia-specific t(15;17). Expression of PML/RARalpha in hematopoietic precursor cell lines induces block of differentiation and promotes survival. We report here that PML/RARalpha has a potent growth inhibitory effect on all nonhematopoietic cell lines and on the majority of the hematopoietic cell lines tested. ...
Acute promyelocytic leukemia (APL) is associated with reciprocal chromosomal translocations always involving the retinoic acid receptor alpha (RARalpha) gene on chromosome 17 and variable partner genes (X genes) on distinct chromosomes. RARalpha fuses to the PML gene in the vast majority of APL cases, and in a few cases to the PLZF, NPM, NuMA and Stat5b genes, respectively, leading to the gener...
Previous studies have demonstrated that combinations of all-trans retinoic acid (ATRA) with either granulocyte-colony stimulating factor (G-CSF) or lithium chloride (LiCl) produced synergistic terminal differentiation of WEHI-3B myelomonocytic leukemia (D(+)) cells. It was found that steady-state retinoic acid receptor alpha (RARalpha) protein levels were markedly reduced in these cells after e...
Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARalpha and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARalpha and NPM-RARalpha. PLZF-RARalpha transgenic animals developed chronic myeloid leukemia-like phenotypes at an e...
Acute promyelocytic leukemia (APL) cells, containing the t(15;17) rearrangement, express the fusion protein, PML/RARalpha. Clinically, patients respond to all-trans retinoic acid (ATRA) through complete remissions associated with myeloid maturation of leukemic cells. This clinical ATRA response of APL is linked to PML/RARalpha expression. Unfortunately, these remissions are transient and relaps...
Expression of the PML-retinoic acid receptor alpha (PML-RARalpha) fusion protein is the initiating genetic event for acute promyelocytic leukemia (APL), but the molecular mechanisms responsible for disease initiation are not yet clear. Several observations have suggested that early myeloid cells are uniquely susceptible to transformation by PML-RARalpha. Recently, we have shown that the early m...
The fusion protein PML-RARalpha, generated by the t(15;17)(q22;q11.2) translocation associated with acute promyelocytic leukemia (APL), initiates APL when expressed in the early myeloid compartment of transgenic mice. PML-RARalpha is cleaved in several positions by a neutral serine protease in a human myeloid cell line; purification revealed that the protease is neutrophil elastase (NE). Immuno...
Signaling through vitamin A metabolites is indispensable for spermatogenesis, and disruption of retinoic acid receptor alpha (RARalpha) function resulted in male sterility and aberrant spermatogenesis, which resembled vitamin A deficiency. Here we investigated the lineage- and cell-specific role of RARalpha-mediated signaling during spermatogenesis using germ-cell transplantation and geneticall...
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