CD133 marks a stem cell population that drives human primary myelofibrosis

Triviai, Ioanna; Stübig, Thomas; Niebuhr, Birte; Hussein, Kais; Tsiftsoglou, Asterios S.; Stocking, Carol

doi:10.3324/haematol.2014.118463

Cited by 13 publications

(12 citation statements)

References 51 publications

(46 reference statements)

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“…Based on prior work there are several proteins including CD133, CD90 and CD24 which may be good markers of PanINs. CD133 is a marker for many stem cells which has been used to identify putative CSC from solid tumors [ 25 – 27 ]. Kazuya S et al reported that CD133 staining was not observed in all stages of PanIN or IPMN and only expressed in PDAC, which indicates that it can differentiate IPMN from PDAC but not PanIN from IPMN [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

CD90 and CD24 Co-Expression Is Associated with Pancreatic Intraepithelial Neoplasias

et al. 2016

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Thy-1 (CD90) has been shown to be a potential marker for several different types of cancer. However, reports on CD90 expression in pancreatic intraepithelial neoplasia (PanIN) lesions are still limited where PanINs are the most important precursor lesion of pancreatic ductal adenocarcinoma (PDAC). Herein, we investigate candidate markers for PanIN lesions by examining the distribution and trend of CD90 and CD24 expression as well as their co-expression in various stages of PanINs. Thirty cases of PanINs, which were confirmed histopathologically and clinically, were used to evaluate protein expression of CD90 and CD24 by immunofluoresence double staining. CD90 was found to be mainly expressed in stroma around lesion ducts while not observed in acini and islets in PanINs. CD90 also showed increased expression in PanIN III compared to PanIN I. CD24 was mainly present in the cytoplasm and membrane of pancreatic ductal epithelia, especially in the apical epithelium of the duct. CD24 had higher expression in PanIN III compared with PanIN II or PanIN I. CD90 was expressed around CD24 sites, but there was little overlap between cells that expressed each of these proteins. A correlation analysis showed that these two proteins have a moderate relationship with PanIN stages respectively. These results suggest that co-expression of CD90 and CD24 may have an important role in the development and progression of PanINs, which is also conducive to early detection and treatment of PDAC.

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Section: Discussionmentioning

confidence: 99%

CD90 and CD24 Co-Expression Is Associated with Pancreatic Intraepithelial Neoplasias

et al. 2016

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“…Several molecular mechanisms and other clues suggest the clonal nature of the disease and that mutational clonal evolution in PMF is dependent on multiple hematopoietic clones [ 22 – 24 ]. The pathological hematopoietic stem cells harbor genetic mutations conferring the proliferative phenotype of the disease.…”

Section: Myeloproliferation and Myelofibrosis: The Dual Complementmentioning

confidence: 99%

“…Mutations can also occur in epigenetic regulator genes such as TET-2 [ 37 ], DNMT3A [ 38 ], or ASXL1 [ 39 ]. Recently, stem cell populations from PMF patients identified by the expression of CD133 have been investigated and after transplantation into mice were able to recapitulate major PMF parameters, revealing that CD133 marks a stem cell population that drives PMF [ 24 ]. However, despite numerous mutations, none are able, as the BCR-ABL mutations in chronic myeloid leukemia, to fully recapitulate the disease in an animal model or to entirely explain the pathophysiological features of PMF.…”

Section: Myeloproliferation and Myelofibrosis: The Dual Complementmentioning

confidence: 99%

Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis

Desterke

Martinaud

Ruzehaji

et al. 2015

Mediators of Inflammation

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Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm where severity as well as treatment complexity is mainly attributed to a long lasting disease and presence of bone marrow stroma alterations as evidenced by myelofibrosis, neoangiogenesis, and osteosclerosis. While recent understanding of mutations role in hematopoietic cells provides an explanation for pathological myeloproliferation, functional involvement of stromal cells in the disease pathogenesis remains poorly understood. The current dogma is that stromal changes are secondary to the cytokine “storm” produced by the hematopoietic clone cells. However, despite therapies targeting the myeloproliferation-sustaining clones, PMF is still regarded as an incurable disease except for patients, who are successful recipients of allogeneic stem cell transplantation. Although the clinical benefits of these inhibitors have been correlated with a marked reduction in serum proinflammatory cytokines produced by the hematopoietic clones, further demonstrating the importance of inflammation in the pathological process, these treatments do not address the role of the altered bone marrow stroma in the pathological process. In this review, we propose hypotheses suggesting that the stroma is inflammatory-imprinted by clonal hematopoietic cells up to a point where it becomes “independent” of hematopoietic cell stimulation, resulting in an inflammatory vicious circle requiring combined stroma targeted therapies.

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“…Hypoxia activated HIF-1α/Twist-Bmi1 axis promote epithelial-mesenchymal transition (EMT) and renal fibrogenesis22. CD133-positive cells could drive chronic and acute phases of primary myelofibrosis in mice23. Sox2-positive skin progenitor cells were found to contribute to bleomycin-induced skin fibrosis24.…”

Section: Discussionmentioning

confidence: 99%

Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

Chang

2016

Sci Rep

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Oral submucous fibrosis (OSF), regarded as a precancerous condition, is characterized by juxta-epithelial inflammatory reaction followed by fibro-elastic change in the lamina properia and epithelial atrophy. The pathologic mechanisms of OSF still need to be further clarified. In the study, we investigated the functional expression of SSEA-4, which is a well-known stemness marker, in myofibroblast activity and the clinical significance in OSF tissues. The expression of SSEA-4 in OSF was evaluated by immunohistochemical staining. Functional analysis of SSEA-4 on myofibroblast activity of OSF was achieved by lentiviral silencing ST3GAL2. Immunohisitochemistry demonstrated that SSEA-4 expression was significantly higher expression in areca quid chewing-associated OSF tissues than those of normal oral mucosa tissues. From flow cytometry analysis, arecoline dose-dependently activated SSEA-4 expression in primary human normal buccal mucosal fibroblasts (BMFs). Sorted SSEA-4-positive cells from fibrotic BMFs (fBMFs) have higher colony-forming unit, collagen gel contraction, and α-smooth muscle actin (α-SMA) expression than SSEA-4-negative subset. Knockdown of ST3GAL2 in fBMFs suppressed SSEA-4 expression, collagen contraction, migration, invasiveness, and wound healing capability. Consistently, silencing ST3GAL2 was found to repress arecoline-induced myofibroblast activity in BMFs. The study highlights SSEA-4 as a critical marker for therapeutic intervention to mediate myofibroblast transdifferentiation in areca quid chewing-associated OSF.

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CD133 marks a stem cell population that drives human primary myelofibrosis

Abstract: MethodsPatients with primary myelofibrosis, normal donor specimens and study approval

Cited by 13 publications

References 51 publications

CD90 and CD24 Co-Expression Is Associated with Pancreatic Intraepithelial Neoplasias

CD90 and CD24 Co-Expression Is Associated with Pancreatic Intraepithelial Neoplasias

Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis

Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis

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