Role of immune responses in the pathogenesis of low‐risk MDS and high‐risk MDS: implications for immunotherapy

Aggarwal, Shikhar; Loosdrecht, Arjan A. van de; Alhan, Canan; Ossenkoppele, Gert J.; Westers, Theresia M.; Bontkes, Hetty J.

doi:10.1111/j.1365-2141.2011.08683.x

Cited by 88 publications

(71 citation statements)

References 177 publications

(186 reference statements)

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“…1 Recent studies implicate NK cells in the control of myelodysplastic syndromes (MDSs), a heterogeneous spectrum of clonal hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and transformation to acute myeloid leukemia (AML). 1,2 Whereas higher NK-cell frequencies have been reported in patients with low-risk MDSs, 3 in high-risk cases, NK cells are reduced, with decreased expression of activating receptors and impaired cytotoxicity. 4,5 Each NK cell can express both activating killer immunoglobulinlike receptors (aKIRs) and inhibitory KIRs that interact to regulate NK-effector function.…”

Section: Introductionmentioning

confidence: 99%

KIR gene haplotype: an independent predictor of clinical outcome in MDS patients

Stringaris

Marín

Barrett

et al. 2016

Blood

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Key Points• KIR haplotype A is an independent risk factor for the progression of MDS to AML.Myelodysplastic syndromes (MDSs) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDSs. Here, we first examined the distribution of aKIR genes and haplotype in 2 independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs 3 genes; P 5 .001), and lower in patients with secondary AML (progressed from MDSs) compared with de novo AML patients (2 vs 3; P 5 .008) and healthy controls (2 vs 3; P 5 .006). In a multivariate analysis, the presence of KIR haplotype A (characterized by low aKIR content 0-1) independently predicted a higher risk of conversion to AML (relative risk [RR] with 95% confidence interval [CI], 2.67 [1.13-6.71]; P 5 .02) and worse adjusted progression-free survival (RR with 95% CI, 2.96 [1.59-5.52]; P 5 .001) and overall survival (2.25 [1.17-4.31]; P 5 .02), compared with KIR haplotype B (multiple aKIR genes). These novel findings may help to identify MDS patients with a high risk of disease progression who would likely benefit from adoptive NK-cell therapy. (Blood. 2016;128(24):2819-2823

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Section: Introductionmentioning

confidence: 99%

KIR gene haplotype: an independent predictor of clinical outcome in MDS patients

Stringaris

Marín

Barrett

et al. 2016

Blood

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“…PA is an autoimmune disease in which Th1 CD4 + T lymphocytes reacting to H + /K + -ATPase in the gastric parietal cells play a role in the pathogenesis and patients with PA are at a high risk of complicating other autoimmune diseases [1,2]; however, our literature search did not detect the association between PA and PMR. On the other hand, it is reported that various immunological abnormalities exist in patients with MDS, such as abnormal antigen presentation, reduced T-cell reaction, abnormal B-cell function, abnormal Band T-cell interaction, reduced number and impaired function of natural killer cells, and impaired function of monocytes [7,15,16]. Furthermore, autoimmune diseases are reported to be complicated in about 10% of MDS patients and the association with PMR has been occasionally reported [8,9,11,12].…”

Section: Discussionmentioning

confidence: 99%

Myelodysplastic Syndrome and Polymyalgia Rheumatica Associated With Pernicious Anemia

Otsuka¹,

Higuchi²,

Nakajima³

et al. 2015

J Hematol

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An 83-year-old man who had been treated for pernicious anemia (PA) developed myelodysplastic syndrome (MDS) and polymyalgia rheumatica (PMR). While PA patients are at an increased risk of malignant tumors, association with MDS is rarely reported. PA patients are also associated with various autoimmune conditions; however, association with PMR has not been reported. Derangement in the immune system associated with PA and subsequent MDS was assumed to have contributed to the development of PMR.

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“…Several additional immune cell populations such as macrophages and natural killer cells have been shown to increase in number and activity in the marrow of patients with low-risk MDS and to decrease as MDS progresses [49]. While perturbations in the B-cell compartment are less studied, B-cell progenitors may be reduced in low-risk MDS [50].…”

Section: Mds Inflammation and Autoimmunity - Putting The Puzzle Togmentioning

confidence: 99%

Autoimmunity and Inflammation in Myelodysplastic Syndromes

Wolach

Stone²

2016

Acta Haematol

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Autoimmune and inflammatory conditions (AICs) are encountered in up to 25% of patients with myelodysplastic syndromes (MDS). A wide range of AICs have been reported in association with MDS and can range from limited clinical manifestations to systemic diseases affecting multiple organs. Vasculitides, connective tissue diseases, and inflammatory arthritis are frequently reported in different studies; noninfectious fever and constitutional symptoms at presentation are common. Associations between AICs and specific MDS characteristics vary by study, but the available data suggest that AICs cluster more often in younger patients with higher-risk MDS. In general, AICs do not seem to confer worse survival, although certain AICs may be associated with adverse outcome (e.g. vasculitis) or progression of MDS (Sweet's syndrome). Nonetheless, these complications may have a significant impact on quality of life and affect the timing and type of MDS-directed therapy. The mainstay of management of these complications in the short term relies on immunosuppressive drugs. Increasing evidence suggests that hypomethylating agents may be effective in treating these complications and reduce steroid dependence. While the pathogenesis of AICs is incompletely understood, growing appreciation of cellular immune deregulation, cytokine hypersecretion, and the genetic heterogeneity underlying MDS may improve our understanding of common pathways linking MDS, inflammation, and autoimmunity.

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Role of immune responses in the pathogenesis of low‐risk MDS and high‐risk MDS: implications for immunotherapy

Cited by 88 publications

References 177 publications

KIR gene haplotype: an independent predictor of clinical outcome in MDS patients

KIR gene haplotype: an independent predictor of clinical outcome in MDS patients

Myelodysplastic Syndrome and Polymyalgia Rheumatica Associated With Pernicious Anemia

Autoimmunity and Inflammation in Myelodysplastic Syndromes

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