Dataset Information

The role of E2A in ATPR-induced cell differentiation and cycle arrest in acute myeloid leukaemia cells.

ABSTRACT: Acute myeloid leukaemia (AML) is a biologically heterogeneous disease with an overall poor prognosis; thus, novel therapeutic approaches are needed. Our previous studies showed that 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), a new derivative of all-trans retinoic acid (ATRA), could induce AML cell differentiation and cycle arrest. The current study aimed to determine the potential pharmacological mechanisms of ATPR therapies against AML. Our findings showed that E2A was overexpressed in AML specimens and cell lines, and mediate AML development by inactivating the P53 pathway. The findings indicated that E2A expression and activity decreased with ATPR treatment. Furthermore, we determined that E2A inhibition could enhance the effect of ATPR-induced AML cell differentiation and cycle arrest, whereas E2A overexpression could reverse this effect, suggesting that the E2A gene plays a crucial role in AML. We identified P53 and c-Myc were downstream pathways and targets for silencing E2A cells using RNA sequencing, which are involved in the progression of AML. Taken together, these results confirmed that ATPR inhibited the expression of E2A/c-Myc, which led to the activation of the P53 pathway, and induced cell differentiation and cycle arrest in AML.

SUBMITTER: Zhang M

PROVIDER: S-EPMC8831953 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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The role of E2A in ATPR-induced cell differentiation and cycle arrest in acute myeloid leukaemia cells.

Zhang Meiju M Wang Long-Fei LF Xu Xiaoling X Du Yan Y Li Lanlan L Deng Ge G Feng Yubin Y Ou Ziyao Z Wang Ke K Xu Yayun Y Peng Xiaoqing X Chen Feihu F

Journal of cellular and molecular medicine 20220109 4

Acute myeloid leukaemia (AML) is a biologically heterogeneous disease with an overall poor prognosis; thus, novel therapeutic approaches are needed. Our previous studies showed that 4-amino-2-trifluoromethyl-phenyl retinate (ATPR), a new derivative of all-trans retinoic acid (ATRA), could induce AML cell differentiation and cycle arrest. The current study aimed to determine the potential pharmacological mechanisms of ATPR therapies against AML. Our findings showed that E2A was overexpressed in A ...[more]

PMID: 35001521

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Project description:BackgroundExposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML). Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells.Case presentationTwo white females (A and B) hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5). The patient did not respond to therapy and died three weeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3). Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987-1993 and 1997-2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently developed symptoms of respiratory irritation and dizziness.ConclusionThe findings support the hypothesis that the specific AML cases might have originated from exposure to chemicals, especially hydroquinone and/or glutaraldehyde. The report also emphasises the crucial role of inspection of facilities and enforcement of compliance with regulations in order to prevent similar incidents.

Dataset Information

The role of E2A in ATPR-induced cell differentiation and cycle arrest in acute myeloid leukaemia cells.

Publications

The role of E2A in ATPR-induced cell differentiation and cycle arrest in acute myeloid leukaemia cells.

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