Prognosis in Myelodysplastic Syndromes: The Clinical Challenge of Genomic Integration

Chen-Liang, Tzu Hua

doi:10.3390/jcm10102052

Cited by 4 publications

(2 citation statements)

References 68 publications

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“…Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid neoplasms characterized by inefficient hematopoiesis, cytopenia, and a high risk of progression to acute myeloid leukemia (AML) [ 1 ]. According to the Revised International Prognosis Scoring System (IPSS-R), the overall survival of very low-risk patients is 8.8 years, while that of very high-risk MDS patients was 0.8 years [ 2 ]. In low-risk MDS patients (IPSS-R very low, low, intermediate), therapy includes recombinant erythropoietin and red blood cell transfusion, and it is mainly aimed at improving cytopenias to prevent complications.…”

Section: Introductionmentioning

confidence: 99%

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling

Zhao

Wang

et al. 2022

Cell Death Discov.

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The factors that affect hypomethylating agents (HMAs) sensitivity in myelodysplastic syndrome (MDS) are complex and multifaceted. They include DNA methylation, gene expression, mutation, etc. However, the underlying mechanisms are still not clearly illustrated. In the present work, ABAT gene expression was associated with HMAs sensitivity. It was found that ABAT gene interference increased the sensitivity of HL-60 and THP-1 cells to HMAs treatment, while ABAT overexpression decreased its sensitivity. RNA-sequencing analysis showed that ABAT knockdown activated both interferon I and interferon-gamma signaling while inhibiting the secondary metabolic synthesis and arginine metabolic process. Gas chromatography-mass spectrometry (GC-MS) based metabolic profiling also demonstrated that ABAT gene knockdown affected arginine, alanine, aspartate, and glutamate metabolism, in addition to the biosynthesis of valine, leucine, and isoleucine, and the metabolism of beta-alanine. The ABAT gene expression downregulation could activate the CXCR4/mTOR signaling pathway, which was related to HMAs sensitivity. CXCR4 expression was regulated by mTOR activity and vice versa. In vivo, mice injected with ABAT gene knockdown cells lived longer than control mice after HMAs treatment. Overall, this study elucidates the novel regulatory mechanisms of HMAs sensitivity and provides a potential therapeutic target in MDS.

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Section: Introductionmentioning

confidence: 99%

ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling

Zhao

Wang

et al. 2022

Cell Death Discov.

View full text Add to dashboard Cite

show abstract

“…Those patients included in the lower-risk subset may benefit from additional stratification by the MD Anderson Lower-risk Prognostic Scoring System (LR-PSS) that shows a better performance than IPSS-R in this population. Cheng-Liang (Department of Hematology, Hospital Universitario Morales Meseguer, Murcia, Spain) offers us a guided review to current MDS prognostication, including the independent contribution of mutational studies [ 5 ].…”

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confidence: 99%