The inflammatory microenvironment in MDS

Yang, Lili; Qian, Yaqin; Eksioglu, Erika A.; Epling-Burnette, Pearlie K.; Wei, Sheng

doi:10.1007/s00018-015-1846-x

Cited by 58 publications

(49 citation statements)

References 82 publications

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“…There is growing evidence for the role of activated innate immunity and inflammation as well as immune deregulation in the pathogenesis of MDS [9,10]. The data from the Swedish registry suggested increased risk of MDS among patients with history of chronic immune stimulation [6].…”

Section: Discussionmentioning

confidence: 99%

Autoimmune diseases and myelodysplastic syndromes

et al. 2016

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Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n 5 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with 5% prevalence included idiopathic thrombocytopenic purpura in 12% (n 5 46), rheumatoid arthritis in 10% (n 5 41), and psoriasis in 7% (n 5 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P 5 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P 5 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n 5 89) in MDS patients with autoimmune disease versus 30% (n 5 301) in those without (P 5 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation.Am. J. Hematol. 91:E280-E283,

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Section: Discussionmentioning

confidence: 99%

Autoimmune diseases and myelodysplastic syndromes

et al. 2016

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“…The pathophysiology lying behind the progression of such diseases is extremely variable and, therefore, classified in a generic way, involving causes related to intrinsic abnormalities in myeloid progenitors and causes related to extrinsic alterations in the BM microenvironment (104, 105). Although the precise connection is still being elucidated, several studies have correlated MDS with inflammatory disorders.…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Stress and Non-Stress Roles of Inflammatory Signals during HSC Emergence and Maintenance

2016

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Hematopoietic stem cells (HSCs) are a rare population that gives rise to almost all cells of the hematopoietic system, including immune cells. Until recently, it was thought that immune cells sense inflammatory signaling and HSCs respond only secondarily to these signals. However, it was later shown that adult HSCs could directly sense and respond to inflammatory signals, resulting in a higher output of immune cells. Recent studies demonstrated that inflammatory signaling is also vital for HSC ontogeny. These signals are thought to arise in the absence of pathogens, are active during development, and indispensable for HSC formation. In contrast, during times of stress and disease, inflammatory responses can be activated and can have devastating effects on HSCs. In this review, we summarize the current knowledge about inflammatory signaling in HSC development and maintenance, as well as the endogenous molecular cues that can trigger inflammatory pathway activation. Finally, we comment of the role of inflammatory signaling in hematopoietic diseases.

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“…Several recent comprehensive reviews have described the systemic and non-cell autonomous consequences of chronic innate immune activation in MDS, including the effects of increased inflammation and abnormal adaptive and innate immunity on BM HSC 16,17 . Herein, we will systematically deconstruct aberrant function of TLR signaling mediators within MDS HSC that may contribute to the cell intrinsic consequences associated with ineffective hematopoiesis and disease pathogenesis (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Deconstructing innate immune signaling in myelodysplastic syndromes

Varney¹,

Melgar²,

Niederkorn³

et al. 2015

Experimental Hematology

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Overexpression of immune-related genes is widely reported in Myelodysplastic syndromes (MDS), and chronic immune stimulation increases the risk for developing MDS. Aberrant innate immune activation, such as due to increased Toll-like receptor (TLR) signaling, in MDS can contribute to systemic effects on hematopoiesis in addition to cell-intrinsic defects on hematopoietic stem/progenitor cell (HSPC) function. This review will deconstruct aberrant function of TLR signaling mediators within MDS HSPC that may contribute to cell intrinsic consequences on hematopoiesis and disease pathogenesis. We will discuss the contribution of chronic TLR signaling to the pathogenesis of MDS based on evidence from patients and mouse genetic models.

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The inflammatory microenvironment in MDS

Cited by 58 publications

References 82 publications

Autoimmune diseases and myelodysplastic syndromes

Autoimmune diseases and myelodysplastic syndromes

Stress and Non-Stress Roles of Inflammatory Signals during HSC Emergence and Maintenance

Deconstructing innate immune signaling in myelodysplastic syndromes

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