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Experimental Hematology

Stina Wichert, Åsa Pettersson, Thomas Hellmark, Åsa Johansson, Markus Hansson
In experimental studies, eosinophils promote survival, proliferation and retention of plasma cells in the bone marrow (BM). The clinical significance of eosinophils in plasma cell disorders (PCD) in humans is largely unknown. This study focuses on frequency and phenotype of eosinophils in BM and peripheral blood (PB) in patients with untreated PCD compared to healthy controls. The amount of eosinophils per se did not correlate to number of BM plasma cells or disease stage. The expression of chemokine receptor 4, of importance for the homing capacity to bone marrow stromal cells, was significantly higher on patients´ eosinophils and increased with disease stage...
July 5, 2018: Experimental Hematology
Clea S Grace, Hanna K A Mikkola, Diana R Dou, Vincenzo Calvanese, Roger E Ronn, Louise E Purton
Hematopoietic stem cells (HSCs) are multipotent cells responsible for the maintenance of the hematopoietic system throughout life. Dysregulation of the balance between HSC self-renewal, death and differentiation can have serious consequences such as myelodysplastic syndromes (MDS) or leukemia. All-trans retinoic acid (ATRA), the biologically active metabolite of vitamin A/retinoic acid (RA), has been shown to have pleiotropic effects on hematopoietic cells, enhancing HSC self-renewal whilst also increasing differentiation of more mature progenitors...
July 4, 2018: Experimental Hematology
Soghra Fatima, Sheng Zhou, Brian P Sorrentino
Abcg2, a member of the ATP-binding cassette transporter family, is expressed in adult hematopoietic stem cells (HSCs) and is required for the side population phenotype of adult bone marrow HSCs as well as other adult tissue-specific stem cells. Lineage tracing in the adult mice using the Abcg2-Cre mouse model showed that Abcg2 marks HSCs, intestinal stem cells and spermatogonial stem cells. It is unclear whether definitive HSCs or their precursors in the early embryonic development can be marked by Abcg2 expression...
June 28, 2018: Experimental Hematology
Sumbal Sumbal, Aneeqa Javed, Bakht Afroze, Hafiza Fizzah Zulfiqar, Faqeeha Javed, Sobia Noreen, Bushra Ijaz
Cancer is characterized by Darwinian evolution and a primary cause of mortality and morbidity around the globe. Over the preceding decade, the treatment of cancer has been markedly improved by many targeted therapies but these treatments have given birth to new challenges and issues. Clonal evolution and tumor heterogeneity accords a significant challenge in designing cancer therapies. Fortunately, these restrictions have been overcome by technological advancements allowing us to track both genetic and epigenetic aberrations...
June 22, 2018: Experimental Hematology
Evert-Jan F M de Kruijf, Rob Zuijderduijn, Marjolein C Stip, Willem E Fibbe, Melissa van Pel
Mesenchymal stromal cells (MSCs) support hematopoietic stem cells (HSCs) in vivo and enhance HSC engraftment and hematopoietic recovery upon cotransplantation with HSCs. These data have led to the hypothesis that MSCs may affect the HSC niche, leading to changes in HSC retention and trafficking. We studied the effect of MSC administration on the HSC compartment in the bone marrow (BM) in mice. After injection of MSCs, HSC numbers in the BM were decreased coinciding with an increased cell cycle activity compared with phosphate-buffered saline (PBS)-injected controls...
June 19, 2018: Experimental Hematology
Kiriko Kaneko, Yoshiko Kubota, Kazumi Nomura, Haruka Hayashimoto, Taisei Chida, Naoto Yoshino, Marina Wayama, Katsutoshi Ogasawara, Yukio Nakamura, Ikuo Tooyama, Kazumichi Furuyama
ALAS2 gene mutations cause X-linked sideroblastic anemia. The presence of ring sideroblasts in a patient's bone marrow is the hallmark of sideroblastic anemia, but the precise mechanisms underlying sideroblast formation are largely unknown. Using a genome editing system, a mutation was introduced in the erythroid-specific enhancer of the ALAS2 gene in HUDEP2 cells, which were derived from human umbilical stem cells and can produce erythrocytes. The established cell line, termed HA2low, expressed less ALAS2 mRNA than did wild-type cells, even after erythroid differentiation...
June 13, 2018: Experimental Hematology
Labiad Yasmine, Venton Geoffroy, Farnault Laure, Baier Céline, Colle Julien, Mercier Cedric, Ivanov Vadim, Nicolino Corinne, Loriod Béatrice, Fernandez-Nunez Nicolas, Torres Magali, Jean-Camille Mattei, Rihet Pascal, Nguyen Catherine, Costello Régis
Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment in multiple myeloma and relapsed or refractory lymphomas. After auto-HSCT, hematologic reconstitution and infectious complications are the main two critical issues. Though many patients develop infectious complications after therapeutic intensification, it remains impossible to predict infection for each individual. The goal of this work was to determine and identify a predictive transcriptomic signature of systemic inflammatory response syndrome (SIRS) and/or sepsis in patients receiving auto-HSCT...
June 7, 2018: Experimental Hematology
Kamel Laribi, Delphine Bolle, Mustapha Alani, Habib Ghnaya, Saga Le Bourdelles, Anne Besançon, Jonathan Farhi, Nathalie Denizon, Alix Baugier de Materre
Iron overload has been associated with poor overall survival in patients with higher-risk myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation, but has not been investigated in higher-risk MDS patients treated with hypomethylating agents. We evaluated the prognostic value of serum ferritin levels at diagnosis in a retrospective analysis of 48 patients with an intermediate 2 or high-risk International Prognostic Scoring System (IPSS) score treated with azacytidine. overall survival probability at 1 and 2years was 58% and 42%, respectively...
June 5, 2018: Experimental Hematology
Yekaterina Galat, Irina Elcheva, Svetlana Dambaeva, Dimantha Katukurundage, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
Improving the understanding of the intricacies of hematopoietic specification of induced or embryonic pluripotent stem cells is beneficial for many areas of research and translational medicine. Currently, it is not clear whether during hPSC hematopoietic differentiation in vitro the maturation of definitive progenitors proceeds through a primitive progenitor (hemangioblast) intermediate or develops independently. The objective of this study is to investigate the early stages of hematopoietic specification of pluripotent stem cells in vitro...
June 4, 2018: Experimental Hematology
Karine Sii-Felice, Marie Giorgi, Philippe Leboulch, Emmanuel Payen
The β-hemoglobinopathies, transfusion-dependent β-thalassemia and sickle cell disease, are the most prevalent inherited disorders worldwide and affect millions of people. Many of these patients have a shortened life expectancy and suffer from severe morbidity despite supportive therapies, which impose an enormous financial burden to societies. The only available curative therapy is allogeneic hematopoietic stem cell transplantation, although most patients do not have an HLA-matched sibling donor, and those who do still risk life-threatening complications...
May 26, 2018: Experimental Hematology
Kyoko Ito, Keisuke Ito
Hematopoietic stem cells maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions and this damage may eventually compromise the cells' self-renewal capacity. Hematopoietic stem cell divisions result in either self-renewal or differentiation, with the balance between the two affecting hematopoietic homeostasis directly; however, the heterogeneity of available hematopoietic stem cells -enriched fractions, together with the technical challenges of observing hematopoietic stem cells behavior, has long hindered the analysis of individual hematopoietic stem cells and prevented the elucidation of this process...
May 25, 2018: Experimental Hematology
Franck Emmanuel Nicolini, Vincent Alcazer, Pascale Cony-Makhoul, Maël Heiblig, Stéphane Morisset, Gaëlle Fossard, Audrey Bidet, Anna Schmitt, Mohamad Sobh, Sandrine Hayette, François-Xavier Mahon, Stéphanie Dulucq, Gabriel Etienne
For the last 15years, imatinib mesylate (IM) has represented the gold standard treatment for chronic-phase chronic myelogenous leukemia (CP-CML); however, outcomes in the very long term remain unknown. We retrospectively analyzed the outcome of 418 IM first-line treated CP-CML patients followed in three reference centers over 15years in and outside of clinical trials, which is believed to represent the "real-life" care of such patients. Molecular analyses were standardized over the years. In case of intolerance or resistance or IM cessation and progression, all clinical data were collected and analyzed...
May 23, 2018: Experimental Hematology
Seerat Elahi, Shawn M Egan, G Aaron Holling, Rachel L Kandefer, Michael J Nemeth, Scott H Olejniczak
Recent biochemical characterization of arsenic resistance protein 2 (Ars2) has established it as central in determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine cap-binding complex, Ars2 promotes cotranscriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture. However, rapidly dividing cells in culture do not represent the physiological condition of the vast majority of cells in an adult mammal...
May 15, 2018: Experimental Hematology
Xiangguo Shi, Ayumi Kitano, Yajian Jiang, Victor Luu, Kevin A Hoegenauer, Daisuke Nakada
Recent advances in next-generation sequencing have identified novel mutations and revealed complex genetic architectures in human hematological malignancies. Moving forward, new methods to quickly generate animal models that recapitulate the complex genetics of human hematological disorders are needed to transform the genetic information to new therapies. Here, we used a ribonucleoprotein-based CRISPR/Cas9 system to model human clonal hematopoiesis of indeterminate potential and acute myeloid leukemia (AML)...
May 8, 2018: Experimental Hematology
Catherine E Jenkins, Samuel Gusscott, Rachel J Wong, Olena O Shevchuk, Gurneet Rana, Vincenzo Giambra, Kateryna Tyshchenko, Rashedul Islam, Martin Hirst, Andrew P Weng
RUNX1 is frequently mutated in T-cell acute lymphoblastic leukemia (T-ALL). The spectrum of RUNX1 mutations has led to the notion that it acts as a tumor suppressor in this context; however, other studies have placed RUNX1, along with transcription factors TAL1 and NOTCH1, as core drivers of an oncogenic transcriptional program. To reconcile these divergent roles, we knocked down RUNX1 in human T-ALL cell lines and deleted Runx1 or Cbfb in primary mouse T-cell leukemias. RUNX1 depletion consistently resulted in reduced cell proliferation and increased apoptosis...
May 5, 2018: Experimental Hematology
Christophe Desterke, Maud Voldoire, Marie-Laure Bonnet, Nathalie Sorel, Sarah Pagliaro, Hind Rahban, Annelise Bennaceur-Griscelli, Emilie Cayssials, Jean-Claude Chomel, Ali G Turhan
The BCR-ABL oncogene, the hallmark of chronic myeloid leukemia (CML), has been shown to activate several signaling pathways in leukemic cells. The natural history of this disease has been radically modified by tyrosine kinase inhibitors (TKIs). However, resistance to several lines of TKI therapies and progression to blast crisis (BC) remain significant concerns. To identify novel signaling pathways induced by BCR-ABL, we performed a transcriptome analysis in a BCR-ABL-expressing UT-7 cell line. More than 2000 genes differentially expressed between BCR-ABL-expressing and parental UT-7 cells were identified and ETS1 was found to be the most upregulated...
May 5, 2018: Experimental Hematology
Sha Si, Yaeko Nakajima-Takagi, Takahito Iga, Mayoko Tsuji, Libo Hou, Motohiko Oshima, Shuhei Koide, Atsunori Saraya, Satoshi Yamazaki, Keiyo Takubo, Yoshiaki Kubota, Tohru Minamino, Atsushi Iwama
Hematopoietic stem cells (HSCs) are exposed to various insults such as genotoxic stress, inflammation, and infection, which have a direct effect. These insults deplete, cause a functional decline in, and promote HSC aging and transformation. However, the impact of hematopoietic insults on niche cells remains largely unknown. We have reported previously that p53 is activated in blood vessels by various stresses, including hypoxia, inflammation, and aging, and contributes to tissue dysfunction and metabolic abnormalities...
April 27, 2018: Experimental Hematology
Lauren A Thurgood, Karen M Lower, Cindy Macardle, Bryone J Kuss
The cryopreservation of peripheral blood mononuclear cells (PBMCs) is a routine research laboratory process, enabling long-term storage of primary patient blood samples. Retrospective analysis of these samples has the potential to identify markers that may be associated with prognosis and response to treatment. To draw valid biological conclusions from this type of analysis, it is essential to ensure that any observed changes are directly related to the pathology of the disease rather than the preservation process itself...
April 26, 2018: Experimental Hematology
Adam C Wilkinson, Maiko Morita, Hiromitsu Nakauchia, Satoshi Yamazaki
Hematopoietic stem cells (HSCs) are used clinically in bone marrow (BM) transplantation due to their unique ability to reform the entire hematopoietic system. Recently, we reported that HSCs are highly sensitive to valine, one of the three branched-chain amino acids (BCAAs) in addition to isoleucine and leucine. Dietary depletion of valine could even be used as a conditioning regimen for HSC transplantation. Here, we report that HSCs are highly sensitive to the balance of BCAAs, with both proliferation and survival reduced by BCAA imbalance...
April 26, 2018: Experimental Hematology
David Azoulay, Yair Herishanu, Mika Shapiro, Yarden Brandshaft, Celia Suriu, Luiza Akria, Andrei Braester
Increased chemokine C-X-C receptor 4 (CXCR4) expression is related to unfavorable outcome in chronic lymphocytic leukemia (CLL). Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that has been shown previously to interact with CXCR4 in neuronal cells. Here, we studied the in vitro effect of BDNF on CXCR4 expression and chemotaxis toward stromal derived factor-1 (SDF-1) in freshly isolated CLL cells. We also explored the correlations between serum BDNF levels in CLL patients and disease characteristics and clinical course...
April 26, 2018: Experimental Hematology
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