Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression

Boysen, Justin C.; Nelson, Michael; Magzoub, G; Maiti, Guru Prasad; Sinha, Sutapa; Goswami, Mousumi; Vesely, Sara K.; Shanafelt, Tait D.; Kay, Neil E.; Ghosh, Asish K.

doi:10.1038/leu.2016.217

Cited by 34 publications

(38 citation statements)

References 42 publications

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“…Previous studies performed in solid and hematological malignancies have already demonstrated a key role of tumor-derived MV in the progression of disease. 30,[43][44][45] In conclusion, based on i) the expression of functional adenosinergic ectoenzymes on malignant cells, ii) the upregulation of these molecules on BM-resident cells, iii) the release of immunosuppressive MV able of amplify ADO production within the BM context, as depicted in Figure 9, the results of this study may delineate a potential immune escape mechanism for metastatic NB. Further studies will evaluate whether CD38, CD39, CD203a/PC-1, and CD73 may represent novel therapeutic targets for highrisk NB patients.…”

Section: Resident Bm Cells As Well As Metastatic Nb Cells)mentioning

confidence: 63%

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

et al. 2019

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Metastatic diffusion of Neuroblastoma (NB) cells in the bone marrow (BM) represents the most negative prognostic factors for NB patients. Multiple immune escape mechanisms are postulated as responsible. Our working hypothesis is that adenosine (ADO), an immunosuppressive molecule along with the ectoenzymatic pathways (CD39-CD73 and CD38-CD203a/PC-1-CD73) controlling its production, are involved in the dynamics of NB cells in the BM. The results indicate that ectonucleotidases are expressed by i) NB cell lines, ii) metastatic NB cells isolated from NB patients' BM, iii) microvesicles (MV) derived from both NB cell types and iv) resident BM cell populations. BM infiltration by NB cells increased CD203a/PC-1 and CD73 expression on lymphoid and myeloid cells, respectively. Expressions of ectoenzymes and GD2 (NB-associated marker) were higher on MV from NB patients' BM than in controls. Moreover, CD203a/PC-1 expression on BM-derived MV provide a basis for distinguishing NB patients with high or low BM infiltration. ADO production and consumption of related by-products were significantly higher when assessed on NB patients' MV than those from controls. MV isolated from NB patients' BM significantly downregulated in vitro T cell proliferation. Lastly, NB patients with worse prognosis are identified by a high percentage of CD38 + or CD73 + MV in the BM. In conclusion, ectonucleotidases are present and functional on NB cells, as well as in NB-infiltrated BM and in MV derived from BM. It is reasonable that MV are involved in BM infiltration by NB cells. Therefore, targeting these molecules may widen the therapeutic armamentarium for metastatic NB patients. ARTICLE HISTORY

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Section: Resident Bm Cells As Well As Metastatic Nb Cells)mentioning

confidence: 63%

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

et al. 2019

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“…The prognostic value of CD52 at protein level has been recognized in the CLL and some malignant lymphomas (12,26). CD52 molecules anchored on the membranes or free in plasma even CD52 + microvesicles in plasma all affect disease prognosis (12,15,26,27). Katharina et al found that CD52 expression on NSCs was correlated with a poor survival in MDS and AML patients with 5q- (13).…”

Section: Discussionmentioning

confidence: 99%

High expression of CD52 predicts poor prognosis of cytogenetic normal acute myeloid leukemia

Cai¹,

Cai²,

Xu³

et al. 2020

Preprint

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Background: The prognosis of cytogenetic normal acute myeloid leukemia (CN-AML) varies. Finding new biomarkers affecting the prognosis of these patients may bring a new strategy for precise classification and treatment. CD52 play a significant role in chronic lymphocytic leukemia (CLL). However, the potential role of CD52 in CN-AML remains largely elusive. Methods: We analyzed the prognostic role of different expression levels of CD52 in 58 CN-AML from The Cancer Genome Atlas (TCGA) dataset and validate these results with 345 CN-AML patients from Gene Expression Omnibus (GEO) dataset. Results: CN-AML patients with high CD52 mRNA expression have a poorer prognosis compared to low CD52 expression ( event-free survival [EFS], P =0.056; overall survival [OS], P=0.043; log-rank test) and the results was verified by GSE12417 (OS, P=0.0197; log-rank test) and GSE71014 (OS, P=0.0197; log-rank test). Hematopoietic stem cell transplantation (HSCT) may improve prognosis of patients with CD52 high . Multivariate cox regression analysis show that the expression level of CD52 (HR=1.503; 95%CI:1.158-1.949 ; P=0.002) was a prognostic factor independent of age (HR=3.045; 95%CI:1.524-6.086; P=0.002) and FLT3 mutation status (HR=2.219; 95%CI:1.123-4.382; P=0.022). CD52 gene expression show a predictive effect on EFS (1-year survival- area under the curve [AUC]:0.685, 2-year survival-AUC:0.752) and OS (1-year survival-AUC: 0.717, 2-year survival-AUC:0.770). Besides, we also found that there is a significant negative correlation between CD52 mRNA expression and DNA methylation . CD52 DNA demethylation may responsible for the high level of CD52 mRNA. Functional enrichment analysis of differentially expressed genes in CD52 high and CD52 low suggests that leukemia cell adhesion-related pathways may be associated with poor prognosis in CD52 high patients . Conclusions: CD52 gene mRNA overexpression is an independent adverse prognostic factor for CN-AML, which could be reversed by HSCT. CD52 DNA demethylation may responsible for the high level of CD52 mRNA. The poor prognosis of patients with CD52 high may involves in leukemia cell adhesion-related pathways. Whether CD52 monoclonal antibodies play a role in high risk patients need further research.

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“…The prognostic value of CD52 at protein level has been recognized in the CLL and some malignant lymphomas (12,26). CD52 molecules or CD52+ microvesicles in plasma all play a role in disease prognosis (12,15,26,27). Katharina et al found that CD52 expression on NSCs was correlated with a poor survival in MDS and AML patients with 5q- (13).…”

Section: Discussionmentioning

confidence: 99%

High expression of CD52 mRNA predicts poor prognosis for cytogenetic normal acute myeloid Leukemia patients

Cai¹,

Cai²,

Xu³

et al. 2020

Preprint

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Background: The prognosis of cytogenetic normal acute myeloid leukemia (CN-AML) varies. Finding new biomarkers affecting the prognosis of these patients may bring a new strategy for precise classification and treatment. CD52 plays a significant role in chronic lymphocytic leukemia (CLL). However, the potential role of CD52 in CN-AML remains largely elusive. Methods: We analyzed the prognostic role of different expression levels of CD52 in 58 CN-AML from The Cancer Genome Atlas (TCGA) dataset and validated these results with 345 CN-AML patients from Gene Expression Omnibus (GEO) dataset. Results: CN-AML patients with high CD52 mRNA expression had a poorer prognosis compared to low CD52 expression ( event-free survival [EFS], P =0.056; overall survival [OS], P=0.043; log-rank test) and the results was verified by GSE12417 (OS, P=0.020; log-rank test) and GSE71014 (OS, P=0.020; log-rank test). Hematopoietic stem cell transplantation (HSCT) may improve prognosis of patients with CD52 high . Regression analysis shows that the expression level of CD52 (HR=1.503; 95%CI:1.158-1.949 ; P=0.002) is a prognostic factor independent of age (HR=3.045; 95%CI:1.524-6.086; P=0.002) and FLT3 mutation status (HR=2.219; 95%CI:1.123-4.382; P=0.022). CD52 gene expression shows a predictive effect on EFS (1-year survival- area under the curve [AUC]:0.685, 2-year survival-AUC:0.752) and OS (1-year survival-AUC: 0.717, 2-year survival-AUC:0.770). Besides, we also found that there is a significant negative correlation between CD52 mRNA expression and DNA methylation . Accordingly, we speculated that CD52 DNA hypomethylation may responsible for the high level of CD52 mRNA. Functional enrichment analysis of differentially expressed genes in CD52 high and CD52 low suggests that adhesion molecule deregulation maybe also the potential pathological mechanism of CD52. Conclusions: CD52 gene mRNA overexpression is an independent adverse prognostic factor for CN-AML. CD52 DNA hypomethylation may responsible for the high level of CD52 mRNA. Adhesion molecule deregulation maybe potential pathological mechanism of CD52. Whether CD52 monoclonal antibodies play a role in high risk patients need further research.

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Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression

Cited by 34 publications

References 42 publications

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

Microvesicles expressing adenosinergic ectoenzymes and their potential role in modulating bone marrow infiltration by neuroblastoma cells

High expression of CD52 predicts poor prognosis of cytogenetic normal acute myeloid leukemia

High expression of CD52 mRNA predicts poor prognosis for cytogenetic normal acute myeloid Leukemia patients

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