Immune dysregulation and potential targeted therapy in myelodysplastic syndrome

Zhang, Xiaoying; Yang, Xiaokui; Ma, Ling; Zhang, Yicheng; Wei, Jia

doi:10.1177/20406207231183330

Cited by 4 publications

(1 citation statement)

References 109 publications

(130 reference statements)

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“…A defining characteristic of cancer cells is their propensity to metastasize, disseminating from local tissues to distant sites(Zhang et al 2023 ). Environmental challenges in these tissues, such as hypoxia, hypoglycemia, growth factor deficiencies, lactic acidosis, oxidative stress, and amino acid starvation, disrupt the precise folding of proteins within the ER(Oakes 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

Yuan,

She,

Jiang

et al. 2024

Mol Med

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The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways—inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER’s protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.

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Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

Yuan,

She,

Jiang

et al. 2024

Mol Med

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Immune‐dysregulation harnessing in myeloid neoplasms

Sharifi,

Xu,

Nasiri

et al. 2024

Cancer Medicine

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Myeloid malignancies arise in bone marrow microenvironments and shape these microenvironments in favor of malignant development. Immune suppression is one of the most important stages in myeloid leukemia progression. Leukemic clone expansion and immune dysregulation occur simultaneously in bone marrow microenvironments. Complex interactions emerge between normal immune system elements and leukemic clones in the bone marrow. In recent years, researchers have identified several of these pathological interactions. For instance, recent works shows that the secretion of inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α), from bone marrow stromal cells contributes to immune dysregulation and the selective proliferation of JAK2V617F+ clones in myeloproliferative neoplasms. Moreover, inflammasome activation and sterile inflammation result in inflamed microenvironments and the development of myelodysplastic syndromes. Additional immune dysregulations, such as exhaustion of T and NK cells, an increase in regulatory T cells, and impairments in antigen presentation are common findings in myeloid malignancies. In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies.

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Real-World Study of the Burden of Myelodysplastic Syndromes in Patients and Their Caregivers in Europe and the United States

Lewis,

Williamson,

Brown

et al. 2024

Oncol Ther

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Introduction Myelodysplastic syndromes (MDS) are characterized by bone marrow failure, peripheral blood cytopenias and a high risk of progression to acute myeloid leukemia (AML), which is associated with a poor prognosis and low survival rates. This study combined surveys with patient chart reviews to document real-world clinical practice and burden of MDS, including perspectives of physicians, patients and caregivers and underlying discrepancies. Methods Physicians in major European countries and the US provided information on 1445 patients, stratified into lower- (LR) and higher-risk (HR) MDS. Patients had the opportunity to complete questionnaires describing the impact of MDS. Caregivers had the option to report on the burden of caring for a patient with MDS. Results While supportive treatment was common, mainly with erythropoietins (52%), anti-AML agents were more frequently used in HR than in LR patients (70% vs 20%), while HR patients generally received more transfusions (48% vs 36%). Symptoms with the largest discordance between patient vs physician reporting were excessive bruising (30% vs 14%), GI side effects (19% vs 6%) and feeling tired or fatigued (68% vs 56%). A bigger impact of fatigue was reported on the European Organization for the Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for HR vs LR patients (43.2 vs 36.5 on a scale from 0 to 100). There was discordance between caregivers vs physicians on reporting of weekly caregiver hours (45.4 vs 29.2) with a Zarit Burden Interview score (ZBI, score 0–88) of 25.4. Conclusions Patients reported a higher frequency than their physicians of top symptoms, with MDS-related disruptions in daily life for both patients and caregivers. There is a need for new therapeutic strategies, along with shared understanding and decision making among patients, caregivers and physicians, to optimize disease management and improve quality of life in people living with MDS. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-024-00303-5.

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Immune dysregulation and potential targeted therapy in myelodysplastic syndrome

Cited by 4 publications

References 109 publications

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

Immune‐dysregulation harnessing in myeloid neoplasms

Real-World Study of the Burden of Myelodysplastic Syndromes in Patients and Their Caregivers in Europe and the United States

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