Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Loss-of-function TET2 mutations (TET2
MT
) are common in myeloid neoplasia. TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. TET2
MT
thus result in hypermethylation and transcriptional repression.
Ascorbic acid
(AA) increases dioxygenase activity by facilitating Fe(III)/Fe(II) redox reaction and may alleviate some biological consequences of TET2
MT
by restoring dioxygenase activity. Here, we report the utility of AA in the prevention of TET2
MT
myeloid neoplasia (MN), clarify the mechanistic underpinning of the TET2-AA interactions, and demonstrate that the ability of AA to restore TET2 activity in cells depends on N- and C-terminal lysine acetylation and nature of TET2
MT
. Consequently, pharmacologic modulation of acetyltransferases and histone deacetylases may regulate TET dioxygenase-dependent AA effects. Thus, our study highlights the contribution of factors that may enhance or attenuate AA effects on TET2 and provides a rationale for novel therapeutic approaches including combinations of AA with class I/II HDAC inhibitor or sirtuin activators in TET2
MT
leukemia
.
...
PMID:Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia. 3289 73
Perfluorooctanesulfonate (PFOS) is a persistent pollutant that can induce toxic effects, including
leukemia
, on blood cells.
Vitamin C
(VC), a functional nutrient, has been found to possess potent cytoprotective effects. However, there are currently no reports on its ability to treat PFOS-associated
leukemia
. This study used a molecular networking analysis to reveal the functional action and pharmacological mechanism of VC against PFOS-associated
leukemia
. The biological informatics findings revealed a total of 17 intersection targets against PFOS-associated
leukemia
. In addition, seven core-functional targets, including tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), sirtuin 1 (SIRT1), nitric oxide synthase 3 (NOS3), myeloid cell
leukemia
-1 (MCL1), and telomerase reverse transcriptase (TERT), were screened and identified. Notably, the molecular docking findings indicated that TP53, MAPK1, and ESR1 were potent pharmacological targets of VC against PFOS-associated
leukemia
. Moreover, the pharmacological functions including biological processes, cell components, and molecular pathways of VC against PFOS-associated
leukemia
were determined. According to the computational findings, we conclude that VC protects against PFOS-associated
leukemia
action by suppressing
leukemia
-associated cell proliferation and tumor growth. The validated genes of TP53, MAPK1, ESR1 may become potential biomarkers for monitoring and treating PFOS-associated
leukemia
.
...
PMID:Functional benefit and molecular mechanism of vitamin C against perfluorooctanesulfonate-associated leukemia. 3329 89
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