CD47 is expressed abnormally on hematopoietic cells in myelodysplastic syndrome

Jiang, Huijuan; Fu, Rong; Wang, Huaquan; Li, Lijuan; Shao, Zonghong

doi:10.1016/j.leukres.2013.04.008

Cited by 42 publications

(40 citation statements)

References 13 publications

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“…It has repeatedly been shown that patients with high-risk myelodysplastic syndrome (MDS) who likely progress to overt AML in the course of their disease express CD47 at higher levels than patients with low-risk MDS [6,16]. Thus, up-regulation of CD47 at the transition from low-risk to high-risk MDS may be one event in the multistep leukemogenesis of MDS.…”

Section: Discussionmentioning

confidence: 99%

“…This CD47 up regulation presumably protects mobilized HSC from subsequent macrophage-mediated phagocytosis [4]. Additionally, CD47 was shown to be of prognostic value in AML as well as in myelodysplastic syndrome (MDS), where CD47 was expressed at higher levels in high-risk as compared to low-risk MDS [6]. In a cohort of 132 AML patients with normal karyotype, high CD47 mRNA levels in peripheral blood blasts were significantly associated with a lower event-free and overall survival [5].…”

Section: Introductionmentioning

confidence: 99%

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CD47 protein expression in acute myeloid leukemia: A tissue microarray-based analysis

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD47 protein expression in acute myeloid leukemia: A tissue microarray-based analysis

et al. 2015

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“…Recent studies report aberrant expression of CD47 in several cancer entities. Tumor cells expressing high levels of CD47 have the ability to escape the innate immune system and therefore survive better than CD47 negative cells in the blood of patients [33–36]. Antibody targeting of CD47 and subsequent reactivation of the innate immune system against transformed cells is showing great promises in pre-clinical studies in different hematological malignancies as well as in sarcoma [37–40].…”

Section: Introductionmentioning

confidence: 99%

Co-expression of MET and CD47 is a novel prognosticator for survival of luminal-type breast cancer patients

et al. 2014

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Although luminal-type primary breast cancer can be efficiently treated, development of metastatic disease remains a significant clinical problem. We have previously shown that luminal-type circulating tumor cells (CTCs) co-expressing the tyrosine-kinase MET and CD47, a ligand involved in cancer cell evasion from macrophage scavenging, are able to initiate metastasis in xenografts. Here, we investigated the clinical relevance of MET-CD47 co-expression in 255 hormone receptor positive breast tumors by immunohistochemistry and found a 10.3-year mean overall-survival difference between MET-CD47 double-positive and double-negative patients (p<0.001). MET-CD47 co-expression defined a novel independent prognosticator for overall-survival by multivariate analysis (Cox proportional hazards model: HR: 4.1, p<0.002) and CD47 expression alone or in combination with MET was strongly associated with lymph node metastasis. Furthermore, flow cytometric analysis of metastatic patient blood revealed consistent presence of MET+CD47+ CTCs (range 0.8 – 33.3% of CTCs) and their frequency was associated with increased metastatic spread. Finally, primary uncultured CTCs with high MET+CD47+ content showed an enhanced capacity to initiate metastasis in mice. Detection and targeting of MET and CD47 may thus provide a rational basis for risk stratification and treatment of patients with luminal-type breast cancer.

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“…Similar up-regulation of CD47 was found in the granulocyte-macrophage progenitor population of patients with myelodysplastic syndrome at the high-risk refractory anemia with excess blasts (RAEB) stage (Pang et al, 2013). Another study found that elevated CD47 on erythroblasts of myelodysplastic syndrome patients positively correlated with their peripheral red blood cell count, consistent with HSC function (Jiang et al, 2013). Association of high CD47 expression with stem cell/tumor-initiating populations has also been reported in gastric cancer (Yoshida, 2015), hepatocellular carcinoma (Lee, 2014b), and pancreatic ductal adenocarcinoma (Cioffi et al, 2015).…”

Section: Cd47 In Cancer Stem Cellsmentioning

confidence: 90%

Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling

Kaur

Roberts

2016

The International Journal of Biochemistry & Cell Biology

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Thrombospondin-1 is a secreted matricellular protein that regulates the differentiation and function of many cell types. Thrombospondin-1 is not required for embryonic development, but studies using lineage-committed adult stem cells have identified positive and negative effects of thrombospondin-1 on stem cell differentiation and self-renewal and identified several thrombospondin-1 receptors that mediate these responses. Genetic studies in mice reveal a broad inhibitory role of thrombospondin-1 mediated by its receptor CD47. Cells and tissues lacking thrombospondin-1 or CD47 exhibit an increased capacity for self-renewal associated with increased expression of the stem cell transcription factors c-Myc, Sox2, Klf4, and Oct4. Thrombospondin-1 inhibits expression of these transcription factors in a CD47-dependent manner. However, this regulation differs in some neoplastic cells. Tumor initiating/cancer stem cells express high levels of CD47, but in contrast to nontransformed stem cells CD47 signaling supports cancer stem cells. Suppression of CD47 expression in cancer stem cells or ligation of CD47 by function blocking antibodies or thrombospondin-1 results in loss of self-renewal. Therefore, the therapeutic CD47 antagonists that are in clinical development for stimulating innate anti-tumor immunity may also inhibit tumor growth by suppressing cancer stem cells. These and other therapeutic modulators of thrombospondin-1 and CD47 signaling may also have applications in regenerative medicine to enhance the function of normal stem cells.

show abstract

CD47 is expressed abnormally on hematopoietic cells in myelodysplastic syndrome

Cited by 42 publications

References 13 publications

CD47 protein expression in acute myeloid leukemia: A tissue microarray-based analysis

CD47 protein expression in acute myeloid leukemia: A tissue microarray-based analysis

Co-expression of MET and CD47 is a novel prognosticator for survival of luminal-type breast cancer patients

Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling

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