Project description:The aim of this study was to gain insight into the potential mechanism of resistance to arsenic trioxide (ATO). The gene expression profile of naive (NB4) (Acute promyelocytic leukemia (APL) cell line and one of its in house generated ATO resistant sub clone (NB4-VM-AsR1) was done using whole genome microarray and compared to generate the differential expression profile which will give insight into the mechanisms of ATO resistance in APL. Agilent one-color experiment,Organism: Human ,Agilent Whole Genome Human 4x44k (AMADID: 014850) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442) naive versus arsenic trioxide resistant acute promyelocytic leukemia cell line NB4
Project description:Acute promyelocytic leukemia (APL) is characterized by the specific chromosome translocation t(15;17) that generates the promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) fusion gene. Arsenic trioxide has been intensively reported to directly and rapidly degrade the PML/RARα fusion protein. Here, we treated NB4 cells (a widely used APL cell line) with arsenic trioxide and performed RNA-seq analysis to identify differentially expressed genes upon arsenic trioxide treatment.
Project description:The aim of this study was to gain insight into the potential mechanism of resistance to arsenic trioxide (ATO). The gene expression profile of naive (NB4) (Acute promyelocytic leukemia (APL) cell line and one of its in house generated ATO resistant sub clone (NB4-VM-AsR1) was done using whole genome microarray and compared to generate the differential expression profile which will give insight into the mechanisms of ATO resistance in APL.
Project description:To further characerize the arsenic trioxide (ATO) resistance in acutepromyelocytic leukemia, we had made NB4 cell line (arsenic sensitive) to be resistant to arsenic by exposing them to increasing concentration till they are resistant to it and we named it NB4-EV-AsR1. We have also used another cell line (UF1) which is by default resistant to arsenic. Comparing the GEP will give us novel pathways that can contirbute to arseic trioxide.
Project description:Acute promyelocytic leukemia (APL) is a hematological disease characterized by a balanced reciprocal translocation that leads to the synthesis of the oncogenic fusion protein PML-RARα. APL is mainly managed by a differentiation therapy based on the administration of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, therapy resistance, differentiation syndrome, and relapses require the development of new low-toxicity therapies based on the induction of blasts differentiation. Here, we performed a high-throughput gene expression profile of the maturation inducible APL cell line NB4 untreated or exposed to ATRA.
Project description:Chemosensitization is an effective strategy to overcome the drawbacks of arsenic trioxide (As2O3) treatment which may be possible through the use of dietary supplements in combination. Proteomic analysis revealed that the combination of arsenic trioxide with vitamins can alter a number of proteins related to the translation, cell cycle, oxidative stress and apoptotic pathways that adds to their effectiveness in the treatment of acute promyelocytic leukemia. This study provides the fact that HL-60 cells became more vulnerable to As2O3 in the presence of L-Ascorbic acid and α-Tocopherol indicating that this combination may be a hopeful approach to increase the outcome of As2O3 in the treatment of acute promyelocytic leukemia.
Project description:Acute promyelocytic leukemia (APL) is categorized as the M3 subtype in the French-American-British classification system. It represents a unique subtype of acute myeloid leukemia (AML) characterized by the t(15;17)/PML::RARA fusion, with leukemic cells arrested at the promyelocytic stage of myelopoiesis. Pediatric APL accounts for approximately 5%-10% of all AML. While the prognosis of APL patients has dramatically improved with the use of all-trans retinoic acid (ATRA) and arsenic trioxide, relapse patients still exist. To reveal the molecular biological basis of pediatric APL, we performed an integrative analysis of the trasncriptome and methylome.
Project description:Acute promyelocytic leukemia (APL) is categorized as the M3 subtype in the French-American-British classification system. It represents a unique subtype of acute myeloid leukemia (AML) characterized by the t(15;17)/PML::RARA fusion, with leukemic cells arrested at the promyelocytic stage of myelopoiesis. Pediatric APL accounts for approximately 5%-10% of all AML. While the prognosis of APL patients has dramatically improved with the use of all-trans retinoic acid (ATRA) and arsenic trioxide, relapse patients still exist. To reveal the molecular biological basis of pediatric APL, we performed an integrative analysis of the trasncriptome and methylome.
Project description:The aim of this study was to gain insight into the potential mechanism of resistance to arsenic trioxide and to identify genes that are modulated in the malignant promyelocytes at the time of relapse in APL patients. We analyzed the gene expression profile by the whole genome microarray of primary promyelocytes obtained from 8 newly diagnosed and 8 at relapse patients. Agilent one-color experiment,Organism: Human ,Agilent Whole Genome Human 4x44k (AMADID: 014850) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442) newly diagnosed versus relapse acute promyelocytic leukemia
Project description:To identify the top 20 up-regulated genes in NB4 TRIB3 shRNA cells in comparison with NB4 control shRNA cells, we examined the microarray gene expression profile of these groups above. Despite the fact that combined therapy of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or chemotherapy dramatically improves the prognosis of patients with acute promyelocytic leukemia (APL), these regimens can cause systemic infections and secondary leukemias. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARa and suppressing its sumoylation, ubiquitylation and degradation. This represses PML nuclear body assembly, p53-mediated senescence, cell differentiation, and supports cellular self-renewal. Genetically inhibiting Trib3 expression or disturbing the TRIB3/PML-RARa interaction produces potent therapeutic efficacy against APL and has synergic anti-APL effects when used in combination with ATRA or ATO by promoting PML-RARa degradation and PML expression. Our study provides new insight into APL pathogenesis and a new therapeutic option against APL.
