Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4+ subset and oligoclonal in the CD8+ subset

Fozza, Claudio; Contini, Salvatore; Galleu, Antonio; Simula, Maria Pina; Virdis, Patrizia; Bonfigli, Silvana; Longinotti, M

doi:10.1016/j.exphem.2009.04.009

Cited by 70 publications

(50 citation statements)

References 32 publications

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“…Increased SREBP signaling in bone marrow and peripheral blood cells of patients with MDS has been associated with poor survival prognosis (50). In addition, it was demonstrated that the activation of the SREBP pathway protects cancer cells from lipotoxicity (51) and promotes growth of activated CD8 ϩ T lymphocytes (52), which expand in MDS patients (53). Through the mevalonate pathway, SREBPs also provide key intermediates required for the isoprenylation of small GTPases, such as farnesylation of Ras and geranylgeranylation of Rho, both involved in cancer progression and metastatic dissemination (54).…”

Section: -Azacytidine Restricts Srebp Activationmentioning

confidence: 99%

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

Poirier

Samami

Mamarbachi

et al. 2014

Journal of Biological Chemistry

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Background:The anticancer drug 5-azacytidine acts through an incompletely understood mechanism. Results: 5-Azacytidine reprograms the glycerolipid biosynthesis pathway and prevents activation of master transcription factors that regulate lipid homeostasis. Conclusion: 5-Azacytidine deeply modifies how cells manage cholesterol and lipid synthesis. Significance: The findings unravel important insights into the mechanism of 5-azacytidine and highlight new potential cancer therapeutics.

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Section: -Azacytidine Restricts Srebp Activationmentioning

confidence: 99%

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

Poirier

Samami

Mamarbachi

et al. 2014

Journal of Biological Chemistry

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“…Peak areas were quantified and normalized with the size marker to determine the total normalized area corresponding to each Vb family. To assess the presence of monoclonal T cell expansions, the relative fluorescence intensity (RI) was calculated: RI (%) = (peak area/total Vb area) (33,34). A CDR3 peak with an RI .…”

Section: Cdr3 Length Analysis By Spectratypingmentioning

confidence: 99%

TCR Bias of In Vivo Expanded T Cells in Pancreatic Islets and Spleen at the Onset in Human Type 1 Diabetes

Codina-Busqueta

Scholz

Torres

et al. 2011

The Journal of Immunology

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Autoreactive T cells, responsible for the destruction of pancreatic β cells in type 1 diabetes, are known to have a skewed TCR repertoire in the NOD mouse. To define the autoreactive T cell repertoire in human diabetes, we searched for intraislet monoclonal expansions from a recent onset in human pancreas to then trace them down to the patient’s peripheral blood and spleen. Islet infiltration was diverse, but five monoclonal TCR β-chain variable expansions were detected for Vβ1, Vβ7, Vβ11, Vβ17, and Vβ22 families. To identify any sequence bias in the TCRs from intrapancreatic T cells, we analyzed 139 different CDR3 sequences. We observed amino acid preferences in the NDN region that suggested a skewed TCR repertoire within infiltrating T cells. The monoclonal expanded TCR sequences contained amino acid combinations that fit the observed bias. Using these CDR3 sequences as a marker, we traced some of these expansions in the spleen. There, we identified a Vβ22 monoclonal expansion with identical CDR3 sequence to that found in the islets within a polyclonal TCR β-chain variable repertoire. The same Vβ22 TCR was detected in the patient’s PBMCs, making a cross talk between the pancreas and spleen that was reflected in peripheral blood evident. No other pancreatic monoclonal expansions were found in peripheral blood or the spleen, suggesting that the Vβ22 clone may have expanded or accumulated in situ by an autoantigen present in both the spleen and pancreas. Thus, the patient’s spleen might be contributing to disease perpetuation by expanding or retaining some autoreactive T cells.

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“…[1]]. Myelodysplastic syndromes (MDS) are clonal hematologic diseases characterized by marked immune dysregulation [2]. Beside the frequent occurrence of clinical manifestations of autoimmune disease, T-cell clones seem to be directly involved in the functional inhibition of hematopoietic precursors [3].…”

Section: Introductionmentioning

confidence: 99%

Patients with Early-Stage Myelodysplastic Syndromes Show Increased Frequency of CD4+CD25<sup>high</sup>+CD127<sup>low</sup> Regulatory T Cells

et al. 2012

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Regulatory T cells (T_reg) have often been ascribed a role in the pathophysiology of several neoplastic diseases considering their potential ability to suppress anti-tumor immunity. This is particularly the case in myelodysplastic syndromes (MDS), which are clonal hematologic disorders characterized by marked immune dysregulation. We analyzed T_reg frequencies in a cohort of 36 patients with early-stage MDS using a flow-cytometric approach based on the concomitant expression of CD25 and CD127. MDS patients showed a higher frequency of CD4+CD25^high+CD127^low T_reg than healthy controls (1.51 vs. 1.14%), with no specific effect of patient- and disease-related factors. Our data point to impaired anti-tumor immunity in patients with MDS, even in the early stage, which has already been noted in other clonal disorders.

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Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4+ subset and oligoclonal in the CD8+ subset

Cited by 70 publications

References 32 publications

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

TCR Bias of In Vivo Expanded T Cells in Pancreatic Islets and Spleen at the Onset in Human Type 1 Diabetes

Patients with Early-Stage Myelodysplastic Syndromes Show Increased Frequency of CD4+CD25<sup>high</sup>+CD127<sup>low</sup> Regulatory T Cells

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