Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

All-trans retinoic reduces the levels of cardiolipins in the NB4 acute promyelocytic leukemia cell-line affecting the autophagy and differentiation responses

ABSTRACT: All-trans retinoic (ATRA) is used in the treatment of acute promyelocytic leukemia a rare form of AML characterized by the presence of a specific translocation involving chrosomes 15;17 and causing the production of the PML-RARα fusion protein in 95% of the cases. ATRA differentiates the APL blasts into neutrophilic granulocytes which are short lived cells. This effect is at the basis of the therapeutic effect of ATRA.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: MARCO BOLIS

PROVIDER: E-MTAB-10267 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Role of cardiolipins, mitochondria, and autophagy in the differentiation process activated by all-trans retinoic acid in acute promyelocytic leukemia.

Gianni' Maurizio M Goracci Laura L Schlaefli Anna A Di Veroli Alessandra A Kurosaki Mami M Guarrera Luca L Bolis Marco M Foglia Marika M Lupi Monica M Tschan Mario P MP Cruciani Gabriele G Terao Mineko M Garattini Enrico E

Cell death & disease 20220110 1

The role played by lipids in the process of granulocytic differentiation activated by all-trans retinoic acid (ATRA) in Acute-Promyelocytic-Leukemia (APL) blasts is unknown. The process of granulocytic differentiation activated by ATRA in APL blasts is recapitulated in the NB4 cell-line, which is characterized by expression of the pathogenic PML-RARα fusion protein. In the present study, we used the NB4 model to define the effects exerted by ATRA on lipid homeostasis. Using a high-throughput lip ...[more]

PMID: 35013142

Similar Datasets

Project description:We defined the RARα interactome in the MDA-MB453 breast cancer cell line genetically engineered to over-express an N-terminally tagged version of the nuclear retinoic acid receptor. Twenty eight nuclear proteins which interact with RARα and whose interaction is stimulated or reduced by the pan-RAR ligand, all-trans retinoic acid (ATRA) were identified. Given the potential significance of the S100A3 calcium-binding protein in the control of tumor progression, we focused our attention on this factor. Using the two models represented by the ATRA-sensitive SKBR3 and MCF7 breast cancer cell lines characterized by constitutive expression of S100A3 and RARα, we demonstrate that the endogenous forms of S100A3 and RARα interact in physiological conditions. The interaction of S100A3 with RARα is cell context independent and it is observed not only in breast cancer but also in acute promyelocytioc leukemia (APL) cells, characterized by expression of the RARα-derived PML-RARα oncogene, which is the product of the t(15:17) chromosomal translocation. S100A3 interacts directly and specifically with RARα and PML-RARα, being unable to bind other members of the RAR/RXR family of retinoid nuclear receptors. The interaction surface maps to the carboxyl-terminal region of the RARα ligand binding domain. Binding of S100A3 to RARα and PML-RARα controls the constitutive and ATRA-dependent degradation of the two receptors. Silencing of the S100A3 gene decreases the amounts of RARα in breast SK-BR-3 and lung A549 cancer cells, rendering them more refractory to the anti-proliferative action of ATRA. In SK-BR-3 cells, this effect is accompanied by a decrease in the lactogenic/differentiating action of ATRA. In APL-derived NB4 cells, S100A3 knock-down reduces the amounts of both RARα and PML-RARα. Contemporaneous down-regulation of the two receptors is associated with an increase in the basal and ATRA-induced expression of many granulocytic differentiation markers. Opposite on RARα and PML-RARα levels as well as ATRA induced differentiation markers are observed upon over-expression of S100A3 in NB4 cells.

Dataset Information

All-trans retinoic reduces the levels of cardiolipins in the NB4 acute promyelocytic leukemia cell-line affecting the autophagy and differentiation responses

Publications

Role of cardiolipins, mitochondria, and autophagy in the differentiation process activated by all-trans retinoic acid in acute promyelocytic leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure