The diverse expression of the<i>WT1</i>gene in patients with acquired bone marrow failure syndromes

You, Yahong; Huo, Jiali; Lu, Shihong; Shao, Yijun; Ge, Meili; Shi, Jun; Li, Xingxin; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Wang, Min; Nie, Neng; Zheng, Yizhou

doi:10.1080/10428194.2017.1352092

Cited by 2 publications

(4 citation statements)

References 32 publications

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“… 30 A former study revealed that bone marrow WT1 level in patients with AA was related to disease severity and could predict the response to immunosuppressive therapy. 22 Our data illustrated that the percentage of MDSC was positively associated with bone marrow WT1 level, which further indicated the involvement of MDSC in the impaired hematopoiesis of AA.…”

Section: Discussionsupporting

confidence: 63%

“…20,21 Our team previously confirmed that WT1 was positively associated with disease severity and clinical outcomes in AA patients. 22 In this study, we discovered that percentages of MDSCs, especially M-MDSCs and eMDSCs, were positively correlated with WT1 level (Figure 2B, Supplemental Figure 2B, C).…”

Section: Relationship Between Mdscs and Clinical Characteristics Of Aamentioning

confidence: 55%

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Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Dong

Chen

et al. 2022

haematol

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Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSCs populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSCs are impaired in AA patients. Decreased percentage of MDSCs, especially monocytic-MDSCs, in the blood of AA patients (n=15) is positively correlated with the frequency of T regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequence analyses reveal that multiple pathways including DNA damage, interleukin (IL)-4, apoptosis, and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSCs of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSCs are defective. Administration of rapamycin significantly increases the absolute number of MDSCs and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSCs from differentiating into mature myeloid cells. These findings reveal that impaired MDSCs are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSCs by rapamycin might provide a promising therapeutic strategy for AA.

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Section: Discussionsupporting

confidence: 63%

Section: Relationship Between Mdscs and Clinical Characteristics Of Aamentioning

confidence: 55%

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Dong

Chen

et al. 2022

haematol

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Section: Introductionmentioning

confidence: 99%

“…Some studies have shown that WT1cn is very low or undetectable in patients with AA at diagnosis and have suggested the potential usefulness of measuring WT1cn in distinguishing AA from MDS [16, 17]. However, the clinical significance of measuring WT1cn in patients with AA remains unclear because previous studies examined PB only in a small number of patients with AA at diagnosis and did not assess the change in WT1cn after treatment.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of the increased expression of the WT1 gene in peripheral blood of patients with acquired aplastic anemia

Ishiyama

Dung

Imi

et al. 2022

eJHaem

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To determine the significance of increased Wilms tumor 1 (WT1) gene expression in the peripheral blood of patients with acquired aplastic anemia (AA), we analyzed serial changes in WT1 mRNA copy number (WT1cn) in 63 patients with AA as well as in five patients with myelodysplastic syndromes (MDS) and seven patients with paroxysmal nocturnal hemoglobinuria (PNH). WT1cn was higher than the cut‐off (≥50 copies/μg RNA) at the time of the first measurement in 41% of untreated (60–190 copies/μg RNA [median 130]) and 59% of treated (59–520 copies/μg RNA [median 150]) AA patients. Although WT1cns gradually increased in most AA patients during the 2–105 months follow‐up period, they did not lead to clonal evolution except in three patients in whom the maximum change ratio of WT1cn (WT1cn‐change max), defined as the ratio of WT1cn at the first examination to that of the maximum value, exceeded 20.0 and who developed MDS at 2, 46, and 105 months. Increased WT1 gene expression was enriched in granulocytes rather than in mononuclear cells in most WT1‐positive AA patients and did not correlate with mutations of genes associated with myeloid malignancy. WT1cns were high at 690–5700 (median 2000) in MDS patients and remained high thereafter, while WT1cns in PNH patients (77–200; median 96) were similar to those in AA. Thus, moderate increases in WT1cns up to 600 are common in AA patients in stable remission. An increase in the WT1cn‐change max over 20.0 may portend transformation from AA to MDS.

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The diverse expression of theWT1gene in patients with acquired bone marrow failure syndromes

Cited by 2 publications

References 32 publications

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Clinical significance of the increased expression of the WT1 gene in peripheral blood of patients with acquired aplastic anemia

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