tretinoin and Leukemia--Biphenotypic--Acute

tretinoin has been researched along with Leukemia--Biphenotypic--Acute* in 2 studies

Other Studies

2 other study(ies) available for tretinoin and Leukemia--Biphenotypic--Acute

ArticleYear
Small molecular modulators of JMJD1C preferentially inhibit growth of leukemia cells.
    International journal of cancer, 2020, 01-15, Volume: 146, Issue:2

    Histone demethylases are promising therapeutic targets as they play fundamental roles for survival of Mixed lineage leukemia rearranged acute leukemia (MLLr AL). Here we focused on the catalytic Jumonji domain of histone H3 lysine 9 (H3K9) demethylase JMJD1C to screen for potential small molecular modulators from 149,519 natural products and 33,765 Chinese medicine components via virtual screening. JMJD1C Jumonji domain inhibitor 4 (JDI-4) and JDI-12 that share a common structural backbone were detected within the top 15 compounds. Surface plasmon resonance analysis showed that JDI-4 and JDI-12 bind to JMJD1C and its family homolog KDM3B with modest affinity. In vitro demethylation assays showed that JDI-4 can reverse the H3K9 demethylation conferred by KDM3B. In vivo demethylation assays indicated that JDI-4 and JDI-12 could induce the global increase of H3K9 methylation. Cell proliferation and colony formation assays documented that JDI-4 and JDI-12 kill MLLr AL and other malignant hematopoietic cells, but not leukemia cells resistant to JMJD1C depletion or cord blood cells. Furthermore, JDI-16, among multiple compounds structurally akin to JDI-4/JDI-12, exhibits superior killing activities against malignant hematopoietic cells compared to JDI-4/JDI-12. Mechanistically, JDI-16 not only induces apoptosis but also differentiation of MLLr AL cells. RNA sequencing and quantitative PCR showed that JDI-16 induced gene expression associated with cell metabolism; targeted metabolomics revealed that JDI-16 downregulates lactic acids, NADP

    Topics: Adult; Aged; Antineoplastic Agents; Apoptosis; Bone Marrow; Cell Line, Tumor; Cell Proliferation; DNA Demethylation; DNA Methylation; Drug Screening Assays, Antitumor; Drug Synergism; Female; Histones; Humans; Jumonji Domain-Containing Histone Demethylases; Leukemia, Biphenotypic, Acute; Male; Middle Aged; Molecular Docking Simulation; Oxidoreductases, N-Demethylating; Protein Domains; Structure-Activity Relationship; Surface Plasmon Resonance; Tretinoin

2020
Function of retinoid acid receptor alpha and p21 in all-trans-retinoic acid-induced acute T-lymphoblastic leukemia apoptosis.
    Leukemia & lymphoma, 2009, Volume: 50, Issue:7

    All-trans-retinoic acid (ATRA) is a morphogenetic signalling molecule derived from vitamin A and is used clinically to target acute promyelocytic leukemia by inducing differentiation of immature blood cells. Retinoid signals are mediated by retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Retinoic acid receptors consist of RARalpha, RARbeta and RARgamma isotypes. Among these components, RARalpha is preferentially bound to ATRA, which is used to treat acute T-lymphoblastic leukemia, yet the conditions and mechanisms remain unknown. In this study, we have demonstrated that, in human acute T-lymphoblastic leukemia Molt3 cells, inhibition of RA-induced proliferation results from massive cell death characterised by apoptosis. The effect of ATRA:RARalpha binding on apoptosis in Molt3 cells has been investigated. Consequently, it has been shown that, in RA-treated Molt3 cells, upregulation of p21 due to RA accompanies caspase 3/PARP activation which precedes the occurrence of apoptosis.

    Topics: Apoptosis; Caspases; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Densitometry; Gene Expression Regulation, Neoplastic; Humans; Leukemia, Biphenotypic, Acute; Models, Biological; Poly(ADP-ribose) Polymerases; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; Tretinoin

2009