Frequent mutations in the ligand-binding domain of PML-RARa after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-trans retinoic acid and histone deacetylase inhibitors in vitro and in vivo
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منابع مشابه
Cytogenetic and FMS-Like Tyrosine Kinase 3 Mutation Analyses in Acute Promyelocytic Leukemia Patients
Background: The secondary genetic changes other than the promyelocytic leukemia-retinoic acid receptor (PML-RARA) fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 (FMS-like tyrosine kinase 3) tyrosine kinase receptor are the frequent genetic alterations in acute myeloid leukemia. However, the prognostic significance of FLT3 mutat...
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Typical acute promyelocytic leukemia (APL) is associated with expression of the PML-RARa fusion protein and responsiveness to treatment with all-trans retinoic acid (ATRA). A rare, but recurrent, APL has been described that does not respond to ATRA treatment and is associated with a variant chromosomal translocation and expression of the PLZFRARa fusion protein. Both PMLand PLZF-RARa possess id...
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Acute promyelocytic leukemia (APL) is characterized by a specific translocation, t(15;17), that fuses the promyelocytic leukemia (PML) gene with the RA receptor RARalpha. Pharmacologic doses of retinoic acid (RA) induce differentiation in human APL cells and complete clinical remissions. Unfortunately, APL cells develop resistance to RA in vitro and in vivo. Recently, mutations in PML/RARalpha ...
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BACKGROUND AND OBJECTIVE Acute promyelocytic leukemia is characterized by the chromosomal translocation t(15;17) which yields the fusion product PML/RARa. All-trans retinoic acid probably induces differentiation of atypical promyelocytes and clinical remission in APL patients by binding to the ligand binding domain (LBD) of the RARa portion of the PML-RARa chimeric protein. Structural alteratio...
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The unique t(15;17) of acute promyelocytic leukemia (APL) retinoid response elements (RAREs). This leads to a dominant negative block of transcription from RAREs that is dosefuses the PML gene with the retinoic acid receptor a (RARa) gene. Although retinoic acid (RA) inhibits cell growth and dependent and not relieved by RA. An unrearranged RARa engineered with this mutation also lost ligand bi...
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