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Integrative Multi-Omics Analysis Unveils the Molecular Mechanisms by Which TP53 Mutation Influence Early Decitabine Resistance in Myelodysplastic Syndrome
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DOI：10.1002/jcb.70076.png)
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Abstract
En 中文
The myelodysplastic syndrome (MDS) is group of clonal hematopoietic stem cell disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular bone marrow, and a high risk of conversion to acute myeloid leukemia. TP53 is a tumor suppressor gene that plays an important role in tumor suppression. Decitabine (DAC) monotherapy has been shown to improve the response rates in TP53-mutated MDS, while the molecular mechanisms of clinical responses are unclear. This study aimed to initially evaluate the TP53 gene locus mutation and the regulation mechanism of DAC on gene expression in AML-MDS cell lines. We detected the mutation of TP53 gene locus in three myeloid tumor cell lines, SKM-1 (mutTP53), M-07e (wtTP53) and HL60 (nullTP53). Then, we performed transcriptomic and proteomic and methylation data in M-07e (wtTP53) and SKM-1 (mutTP53) cells and screened out LGALS1, which is a poor prognostic indicator, as the potential target of TP53 by comparing analysis. We uncovered 31 potential key genes showing differential early responses to DAC treatment in TP53-mutant versus wild-type cells, which may be associated with resistance development. This study revealed the potential molecular mechanisms of TP53 gene locus mutation in DAC-treated MDS.
Keywords:
cell transcriptome
decitabine
DNA methylation
myelodysplastic syndrome
proteome
TP53 mutation
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