Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis
                        and Differentiation in Disease Initiation and Progression

Bar, Merav; Stirewalt, Derek L.; Pogosova-Agadjanyan, Era L.; Wagner, Vitas E.; Gooley, Ted; Abbasi, Nissa; Bhatia, Ravi; Deeg, H. Joachim; Radich, Jerald P.

doi:10.4137/tog.s770

Cited by 6 publications

(1 citation statement)

References 60 publications

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“…In our study, RARα expression was elevated in the blood samples of patients with MDS as compared to healthy volunteers. Earlier, Bar et al using oligonucleotide microarrays, found a statistically significant increase in the expression of genes involved in the RAR-RXR pathway in mononuclear cells from patients with advanced MDS disease as compared to patients with refractory anemia (31). When RARα expression in different risk groups of MDS patients was compared, no statistically significant difference in RARα expression between these groups was found.…”

Section: Discussionmentioning

confidence: 92%

Clinical Relevance of DifferentialRARαandPPARβ/δExpression in Myelodysplastic Syndromes

KALITIN,

DUDINA,

KOSTRITSA

et al. 2024

In Vivo

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Background/Aim: Myelodysplastic syndromes (MDS) are clinically heterogeneous hematological malignancies with an increased risk of transformation to acute myeloid leukemia, emphasizing the importance of identifying new diagnostic and prognostic markers. This study sought to investigate the predictive ability of all-trans retinoic acid (ATRA)-dependent nuclear transcription factors RARα and PPARβ/δ gene expression in MDS patients. Materials and Methods: Peripheral blood specimens were collected from 49 MDS patients and 15 healthy volunteers. The specimens were further separated in Ficoll density gradient to obtain the mononuclear cells fractions. Gene expression analysis was carried out using quantitative real-time polymerase chain reaction (qRT-PCR) technique.Results: In the mononuclear cell fractions of MDS patients, RARα expression was increased (p<0.05) and PPARβ/δ expression was decreased (p<0.01) compared to healthy volunteers. When RARα and PPARβ/δ expression was compared in groups of MDS patients with different risks of disease progression, no statistically significant difference was found for RARα expression, while PPARβ/δ expression was significantly lower in the high-risk group of patients compared to the low-risk group (p<0.05). The expression of RARα was significantly associated with overall survival (p<0.05). ROC analysis showed that the expression of PPARβ/δ, rather than RARα expression, could have potential diagnostic value for MDS patients (AUC=0. 75, p=0.003 and AUC=0.65, p=0.081, respectively). Conclusion: RARα and PPARβ/δ genes are putative biomarkers that may be associated with the diagnosis and prognosis of MDS.

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Section: Discussionmentioning

confidence: 92%

Clinical Relevance of DifferentialRARαandPPARβ/δExpression in Myelodysplastic Syndromes

KALITIN,

DUDINA,

KOSTRITSA

et al. 2024

In Vivo

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The inflammatory microenvironment in MDS

Yang

Qian

Eksioglu

et al. 2015

Cell. Mol. Life Sci.

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Myelodysplastic syndromes (MDS) are a collection of pre-malignancies characterized by impaired proliferation and differentiation of hematopoietic stem cells and a tendency to evolve into leukemia. Among MDS's pathogenic mechanisms are genetic, epigenetic, apoptotic, differentiation, and cytokine milieu abnormalities. Inflammatory changes are a prominent morphologic feature in some cases, with increased populations of plasma cells, mast cells, and lymphocytes in bone marrow aspirates. Accumulating evidence suggests that the bone marrow microenvironment contributes to MDS disease pathology, with microenvironment alterations and abnormality preceding, and facilitating clonal evolution in MDS patients. In this review, we focus on the inflammatory changes involved in the pathology of MDS, with an emphasis on immune dysfunction, stromal microenvironment, and cytokine imbalance in the microenvironment as well as activation of innate immune signaling in MDS patients. A better understanding of the mechanism of MDS pathophysiology will be beneficial to the development of molecular-targeted therapies in the future.

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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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Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression

Cited by 6 publications

References 60 publications

Clinical Relevance of DifferentialRARαandPPARβ/δExpression in Myelodysplastic Syndromes

Clinical Relevance of DifferentialRARαandPPARβ/δExpression in Myelodysplastic Syndromes

The inflammatory microenvironment in MDS

Deconstructing innate immune signaling in myelodysplastic syndromes

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