Immune Dysregulation and Recurring Mutations in Myelodysplastic Syndromes Pathogenesis

Matos, Anacélia Gomes de; Magalhães, Sílvia Maria Meira; Rauh, Michael J.

doi:10.1007/5584_2020_608

Cited by 3 publications

(7 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In clinical settings, patients with an IPSS-R score of 3.5 or less represent a lower-risk MDS group (median survival; 5.9 years), whereas an IPSS-R score > 3.5 falls into the higher-risk MDS group (median survival; 1.5 years) [ 55 ]. The lower-risk disease is associated with an inflammatory microenvironment and increased cell death, in contrast to higher-risk disease, which is delineated by immunosuppression and clonal expansion ( Figure 1 ) [ 7 , 56 ]. Herein, the role of inflammation and immunosuppression regarding their constituting cell types will be discussed.…”

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

“…Aberrant innate immune system activation leads to dysfunctional hematopoiesis and induces excessive cellular death; a hallmark of MDS [ 56 ]. Several factors, intrinsic and extrinsic of the malignant clone, contribute to the intricate inflammatory network.…”

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

“…Aberrancy in the cytokine network has been observed in MDS patients by several investigators [ 8 , 56 , 68 ], with increased levels of inflammatory cytokines, such as TNFa, IFN-γ, TGF-β, IL-6, and IL-8, indicating abnormal inflammatory signaling and myeloid differentiation [ 8 ]. Various cell types can secrete cytokines in MDS, such as myeloid-derived suppressor cells (MDSCs) and MDS-derived myeloid cells [ 5 ].…”

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

“…Various cell types can secrete cytokines in MDS, such as myeloid-derived suppressor cells (MDSCs) and MDS-derived myeloid cells [ 5 ]. Cytokine pressure from chronic immune stimulation has toxic effects on normal HSCs and may provide an evolutionary edge in MDS clones, driving their expansion [ 56 ]. In a first-of-its-kind meta-analysis, Xin et al showed an increased level of inflammatory cytokines implicated in MDS pathogenesis and a cytokine profile changing along with the natural history of the disease [ 69 ].…”

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

“…Low-risk disease and its pyroptotic/ inflammatory microenvironment are associated with elevated levels of inflammatory cytokines (TNFa, IL-6, IFN-γ) [ 70 ] and type 1 cytokines (IL-1β, IL-7, IL-8), whereas high-risk disease has increased immunosuppressive cytokines (like IL-10), reflecting tumor immune escape [ 71 ]. Moreover, a positive correlation can be made between cytokine expression, clinical outcomes [ 56 ], and cytogenetic features [ 68 ].…”

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

See 4 more Smart Citations

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Barakos

Hatzimichael

2022

Diseases

View full text Add to dashboard Cite

Bone marrow, besides the known functions of hematopoiesis, is an active organ of the immune system, functioning as a sanctuary for several mature immune cells. Moreover, evidence suggests that hematopoietic stem cells (the bone marrow’s functional unit) are capable of directly sensing and responding to an array of exogenous stimuli. This chronic immune stimulation is harmful to normal hematopoietic stem cells, while essential for the propagation of myeloid diseases, which show a dysregulated immune microenvironment. The bone marrow microenvironment in myelodysplastic syndromes (MDS) is characterized by chronic inflammatory activity and immune dysfunction, that drive excessive cellular death and through immune evasion assist in cancer cell expansion. Acute myeloid leukemia (AML) is another example of immune response failure, with features that augment immune evasion and suppression. In this review, we will outline some of the functions of the bone marrow with immunological significance and describe the alterations in the immune landscape of MDS and AML that drive disease progression.

show abstract

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

Section: The Immune Landscape In Mdsmentioning

confidence: 99%

See 3 more Smart Citations

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Barakos

Hatzimichael

2022

Diseases

View full text Add to dashboard Cite

show abstract

Molecular Threat of Splicing Factor Mutations to Myeloid Malignancies and Potential Therapeutic Modulations

Zhang

Chen

2022

Biomedicines

View full text Add to dashboard Cite

Splicing factors are frequently mutated in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations are presumed to contribute to oncogenic transformation, but the underlying mechanisms remain incompletely understood. While no specific treatment option is available for MDS/AML patients with spliceosome mutations, novel targeting strategies are actively explored, leading to clinical trials of small molecule inhibitors that target the spliceosome, DNA damage response pathway, and immune response pathway. Here, we review recent progress in mechanistic understanding of splicing factor mutations promoting disease progression and summarize potential therapeutic strategies, which, if successful, would provide clinical benefit to patients carrying splicing factor mutations.

show abstract

Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes

Zhang¹,

Huang²,

Xv³

et al. 2022

Current Oncology

View full text Add to dashboard Cite

Myelodysplastic syndrome is one of the main hematological malignancies that threaten the health of the elderly. However, biomarkers which predict the progression and prognosis of MDS are still controversial and puzzling. FOXO1 gene plays an important role in a variety of intracellular functions, including tumor suppression and cellular immune regulation. However, there is no research report on the correlation between FOXO1 and the clinical features of MDS including immune environment. In this study, we observed that FOXO1 expression is associated with neutrophil count, blasts, chromosome and different MDS scoring systems. FOXO1 expression is closely related to MDS cell immune polarization, and the increase expression of FOXO1 is significantly related to the amplification of immune cell polarization ratio. In addition, FOXO1 expression is associated with progression-free survival and overall survival in MDS patients. Moreover, in a multivariate model FOXO1 low-expression was an independent predictor of poor survival in MDS. In summary, FOXO1 may play a candidate tumor suppressor in MDS, and FOXO1 is a useful independent prognostic predictor in MDS, and it may provide a candidate target therapy in future.

show abstract

Immune Dysregulation and Recurring Mutations in Myelodysplastic Syndromes Pathogenesis

Cited by 3 publications

References 69 publications

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Molecular Threat of Splicing Factor Mutations to Myeloid Malignancies and Potential Therapeutic Modulations

Decreased FOXO1 Expression Is Correlated with Poor Prognosis in Myelodysplastic Syndromes

Contact Info

Product

Resources

About