Set7 Is Highly Expressed in B-Lineage Acute Lymphoblastic Leukemia Cells and Overexpression of Set7 Exhibits Antileukemia Effect

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5088-5088
Author(s):  
Xiao-Tong Ma ◽  
Ya-Kun Mou ◽  
Yang-Yang Zhao ◽  
Nan Wang ◽  
Xiao-Yan Liu ◽  
...  

Abstract Set7 is a member of protein lysine methyltransferase family that is highly conserved in vertebrates. Set7 can regulate the maintenance of chromosome structure, cell cycle and apoptosis, and plays an important role in many kinds of cancer, metabolism and inflammatory process. However, studies concerning its pathogenic role in leukemia are scarce. We analyzed the expression of Set7 in different types of leukemia and healthy human bone marrow cells or peripheral blood from the Oncomine databases (http://www.oncomine.org), and showed that Set7 was highly expressed in acute lymphoid leukemia (ALL) patients, especially in patients with B-ALL. In this study, we examined the expression of Set7 in various hematopoietic tumor cell lines, bone marrow samples from patients and healthy volunteers. We found that Set7 was highly expressed in B-ALL cell lines Nalm6 and REH compared with other hematopoietic malignant cell lines. Furthermore, Set7 was overexpressed in bone marrow mononuclear cells of adult and pediatric patients with B-ALL than in healthy human bone marrow samples, and sorted CD19+ cells, as well (P<0.001). To investigate Set7 gene function, retroviral-mediated overexpression or removal experiments were performed. Gain-of-function and loss-of-function analyses in Nalm6 and REH cells demonstrated that Set7 inhibited cell growth, colony formation and enhanced the chemosensitivity of B-ALL cells to Vincristine (VCR), Arabinocytidine (Ara) and Daunorubicin (DNR). Protein sequence analysis showed that Ebf1 might be a potential substrate for Set7. The expression of Rad51 and Tnsf11, the downstream target genes of Ebf1, were changed as expected when Set7 was overexpressed in Nalm6 and REH. Our study shows for the first time that overexpression of Set7 has an inhibitory effect on B-ALL. These findings suggest that Set7 may be a promising molecular therapy target for B-ALL treatment and provide new clues for understanding the molecular mechanisms of the leukemogenesis of B-ALL. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1740-1748 ◽  
Author(s):  
G Klein ◽  
CA Muller ◽  
E Tillet ◽  
ML Chu ◽  
R Timpl

Collagen type VI, which forms characteristic microfibrillar structures, is assembled from three individual alpha(VI) chains that form a short triple helix and two adjacent globular domains. Expression of all three alpha (VI) collagen chains in the human bone marrow (BM) microenvironment could be detected by chain-specific antibodies in tissue sections and in the adherent stromal layer of long-term BM cultures. In functional studies, collagen type VI was shown to be a strong adhesive substrate for various hematopoietic cell lines and light-density BM mononuclear cells. The adhesive site within the molecule seems to be restricted to the triple helical domain of all three alpha (VI) chains, because individual alpha (VI) chains were not active in the attachment assays. Adhesion of the hematopoietic cell lines to collagen VI was dose-dependent and could be inhibited by heparin. Although the triple helix contains several RGD sequences, adhesion of the hematopoietic cell types to collagen VI could be blocked neither by RGD-containing peptides nor by a neutralizing antibody to the beta 1 integrin subunit. In combination with an antiadhesive substrate, the binding properties of collagen VI could be downregulated. These data suggest that this collagen type may play an important role in the adhesion of hematopoietic cells within the BM microenvironment.


2000 ◽  
Vol 30 (7) ◽  
pp. 618-629 ◽  
Author(s):  
Rood ◽  
Calafat ◽  
Kr. Von dem Borne ◽  
Gerritsen ◽  
Van Der Schoot

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Soukaina Bahsoun ◽  
Karen Coopman ◽  
Elizabeth C. Akam

Abstract Background The effects of cryopreservation on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are still ill-defined. In this study, a quantitative approach was adopted to measure several post-thaw cell attributes in order to provide an accurate reflection of the freezing and thawing impact. Methods Fresh and cryopreserved passage-matched cells from three different donors were discretely analysed and compared for their viability, apoptosis level, phenotypic marker expression, metabolic activity, adhesion potential, proliferation rate, colony-forming unit ability (CFUF) and differentiation potentials. Results The results of this study show that cryopreservation reduces cell viability, increases apoptosis level and impairs hBM-MSC metabolic activity and adhesion potential in the first 4 h after thawing. At 24 h post-thaw, cell viability recovered, and apoptosis level dropped but metabolic activity and adhesion potential remained lower than fresh cells. This suggests that a 24-h period is not enough for a full recovery. Beyond 24 h post-thaw, the observed effects are variable for the three cell lines. While no difference is observed in the pre- and post-cryopreservation proliferation rate, cryopreservation reduced the CFUF ability of two of the cell lines and variably affected the adipogenic and osteogenic differentiation potentials of the three cell lines. Conclusion The data collected in this study clearly show that fresh and cryopreserved hBM-MSCs are different, and these differences will inevitably introduce variabilities to the product and process development and subsequently imply financial losses. In order to avoid product divergence pre- and post-cryopreservation, effective strategies to mitigate freezing effects must be developed and implemented.


1997 ◽  
Vol 148 (2) ◽  
pp. 147-151 ◽  
Author(s):  
S. Iacovacci ◽  
L. Bertolini ◽  
A. Manzin ◽  
M.B. Valli ◽  
M. Battaglia ◽  
...  

Blood ◽  
2015 ◽  
Vol 125 (11) ◽  
pp. 1739-1748 ◽  
Author(s):  
Henrik E. Mei ◽  
Ina Wirries ◽  
Daniela Frölich ◽  
Mikael Brisslert ◽  
Claudia Giesecke ◽  
...  

Key Points Healthy human BM is enriched for PC lacking CD19 that express a prosurvival and distinctly mature phenotype. CD19− PC resist mobilization into blood during immune responses after vaccination as well as B-cell depletion with rituximab.


1991 ◽  
Vol 148 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Shin Aizawa ◽  
Makoto Yaguchi ◽  
Masaru Nakano ◽  
Sadaki Inokuchi ◽  
Hiroshi Handa ◽  
...  

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