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Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - May 18, 2018 Category: Hematology Source Type: research

The RNA binding protein Ars2 supports hematopoiesis at multiple levels
Arsenic resistance protein 2 (Ars2) is an essential, highly conserved protein with mammals sharing more than 98% amino acid identity [1]. Ars2 was initially described as a modulator of arsenic sensitivity in a cDNA screen [2]; subsequent analysis determined that the ability of Ars2 to modulate arsenic sensitivity likely resulted from a dominant-negative effect of the partial cDNA sequence used in the screen [3]. Full length Ars2 did not impart arsenic resistance, but rather was found to be a component of the 5 ’-7-methylguanosine (7mG) cap binding complex (CBC) that coordinated RNA polymerase II (RNAPII) transcriptio...
Source: Experimental Hematology - May 15, 2018 Category: Hematology Authors: Seerat Elahi, Shawn M. Egan, G. Aaron Holling, Rachel L. Kandefer, Michael J. Nemeth, Scott H. Olejniczak Source Type: research

Mesenchymal stromal cells induce a permissive state in the bone marrow that enhances G-CSF-induced hematopoietic stem cell mobilization in mice
Hematopoietic stem cells (HSC) replenish the peripheral blood (PB) cell pool throughout life. During homeostasis, the vast majority of HSC reside in specialized niches, located in the perivascular area of the trabeculated region of the bone marrow (BM). This HSC microenvironment regulates self-renewal, cell cycle entry and differentiation of HSC and consists of a complex network of hematopoietic and non-hematopoietic cells. (reviewed in [1,2]). (Source: Experimental Hematology)
Source: Experimental Hematology - May 15, 2018 Category: Hematology Authors: Evert-Jan F.M. de Kruijf, Rob Zuijderduijn, Marjolein C. Stip, Willem E. Fibbe, Melissa van Pel Source Type: research

Clonal expansion and myeloid leukemia progression modeled by multiplex gene editing of murine hematopoietic progenitor cells
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). (Source: Experimental Hematology)
Source: Experimental Hematology - May 8, 2018 Category: Hematology Authors: Xiangguo Shi, Ayumi Kitano, Yajian Jiang, Victor Luu, Kevin A. Hoegenauer, Daisuke Nakada Source Type: research

Experimental and integrative analyses identify an ETS1 network downstream BCR-ABL in chronic myeloid leukemia (CML)
Chronic myeloid leukemia (CML) accounts for approximately 15% of the newly diagnosed cases of leukemia in adults (1). The BCR-ABL1 fusion gene resulting from the t (9;22) chromosomal translocation is expressed in all CML cells. It encodes the BCR-ABL protein, which is required for oncogenic transformation (2,3). BCR-ABL is a constitutively active tyrosine kinase that promotes the proliferation and survival of leukemic cells through several downstream well-known effectors such as RAS, MYC, and STAT (4 –6). (Source: Experimental Hematology)
Source: Experimental Hematology - May 4, 2018 Category: Hematology Authors: Christophe Desterke, Maud Voldoire, Marie-Laure Bonnet, Nathalie Sorel, Sarah Pagliaro, Hind Rahban, Annelise Bennaceur Griscelli, Emilie Cayssials, Jean-Claude Chomel, Ali G Turhan Tags: Malignant Hematopoiesis Source Type: research

RUNX1 promotes cell growth in human T-cell acute lymphoblastic leukemia by transcriptional regulation of key target genes
The RUNX1 gene, a member of the RUNT-related transcription factor family, is dysregulated in many types of hematologic malignancy [1]. It was first identified as a partner with ETO in t(8;21) acute myelogenous leukemia (AML), and later with TEL/ETV6 in t(12;21) B-lineage acute lymphoblastic leukemia and with EVI1/MECOM in t(3;21) therapy-related AML/myelodysplastic syndrome (MDS). Point mutations and small indels in RUNX1 have been described in MDS/AML and familial platelet disorder with associated myeloid malignancy [2] and more recently in T-cell acute lymphoblastic leukemia (T-ALL) [3 –6]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 4, 2018 Category: Hematology Authors: Catherine E. Jenkins, Samuel Gusscott, Rachel J. Wong, Olena O. Shevchuk, Gurneet Rana, Vincenzo Giambra, Kateryna Tyshchenko, Rashedul Islam, Martin Hirst, Andrew P. Weng Tags: Malignant Hematopoiesis Source Type: research

Hematopoietic insults damage bone marrow niche by activating p53 in vascular endothelial cells
During the lifetime of an animal, hematopoietic stem cells (HSCs) are exposed to various insults, such as genotoxic stress, inflammation, and infection, which directly affect HSCs. These insults deplete HSCs and cause a functional decline in HSCs, and also promote their aging and transformation [1 –3]. However, the impact of hematopoietic insults on niche cells remains largely unknown. (Source: Experimental Hematology)
Source: Experimental Hematology - April 27, 2018 Category: Hematology Authors: 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 Tags: Regular article Source Type: research

Aberrant detection of phenotypic markers in chronic lymphocytic leukemia (CLL) lymphocytes following cryopreservation
In a diagnostic setting, quantifying the expression of membrane proteins by flow cytometry is generally carried out using fresh blood samples where the conformation of the epitope is likely to be in its native form. However, in a research environment, cells such as peripheral blood mononuclear cells (PBMCs) are often cryopreserved in liquid nitrogen and analysed as needed. Cryogenic preservation requires the addition of cryoprotective reagents, most commonly, dimethyl sulfoxide (DMSO), in order to protect the cells from damage during the preservation process1. (Source: Experimental Hematology)
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: Lauren A. Thurgood, Karen M. Lower, Cindy Macardle, Bryone J. Kuss Tags: Brief Communication Source Type: research

Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity
Bone marrow (BM) or hematopoietic stem cell (HSC) transplantation (HSCT) is a potentially curative treatment for a range of hematological disorders, such as immunodeficiency diseases (Copelan,  2006). However, “space” within the recipient's HSC niche (Morrison and Scadden, 2014, Boulais and Frenette, 2015) must be first made to allow donor HSCs to engraft (Czechowicz et al., 2007). Unfortunately, morbidity and mortality associated with traditional BM conditioning regimens, radiatio n and/or chemotherapy, currently limit the application of HSCT (Gyurkocza and Sandmaier, 2014). (Source: E...
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: Adam C Wilkinson, Maiko Morita, Hiromitsu Nakauchi, Satoshi Yamazaki Tags: Brief Communication Source Type: research

Elevated serum BDNF levels are associated with favorable outcome in CLL patients: Possible link to CXCR4 downregulation
CXCR4 is an important and broadly expressed chemokine receptor that is involved in neuronal and hematopoietic cell migration [1]. The well-known ligand for CXCR4, Stromal Derived Factor-1 (SDF1), is a potent chemoattractant that is constitutively expressed by fibroblastic stromal cells and regulates lymphocyte trafficking and extravasation of mononuclear cells [2]. Chronic lymphocytic leukemia (CLL) cells were previously shown to overexpress CXCR4 [3]. Overexpression of CXCR4 in CLL cells was suggested to increase avidity and tropism of the malignant cells to the hematopoietic and lymphatic tissues, leading to lymph node a...
Source: Experimental Hematology - April 26, 2018 Category: Hematology Authors: David Azoulay, Yair Herishanu, Mika Shapiro, Yarden Brenshaft, Celia Suriu, Luiza Akria, Andrei Braester Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - April 25, 2018 Category: Hematology Source Type: research

Synergistic action of dual IGF1/R and MEK inhibition sensitizes childhood acute lymphoblastic leukemia (ALL) cells to cytotoxic agents and involves downregulation of STAT6 and PDAP1
Although cure rates for childhood acute lymphoblastic leukemia (ALL) have increased dramatically over recent years through the integration of risk stratification into treatment protocols [1 –3], failure of remission-inducing therapy is associated with only a 30% 10-year survival rate [4] and relapsed ALL remains the most common cause of cancer-related death in children [5–7]. There is a need for new therapeutic approaches with minimal toxicities for higher-risk leukemias. (Source: Experimental Hematology)
Source: Experimental Hematology - April 12, 2018 Category: Hematology Authors: Victoria J. Weston, Wenbin Wei, Tatjana Stankovic, Pamela Kearns Source Type: research

Synergistic Action of Dual IGF1/R and MEK Inhibition Sensitizes Childhood Acute Lymphoblastic Leukaemia (ALL) Cells to Cytotoxic Agents and Involves Down-Regulation of STAT6 and PDAP1
Although cure rates for childhood ALL have increased dramatically over recent years through the integration of risk-stratification into treatment protocols [1-3], failure of remission-inducing therapy is associated with only a 30% ten-year survival rate [4] and relapsed ALL remains the commonest cause of cancer-related death in children [5-7]. There is a need for new therapeutic approaches with minimal toxicities for higher-risk leukaemias. (Source: Experimental Hematology)
Source: Experimental Hematology - April 12, 2018 Category: Hematology Authors: Victoria J Weston, Wenbin Wei, Tatjana Stankovic, Pamela Kearns Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - April 11, 2018 Category: Hematology Source Type: research

The physical and cellular conditions of the human pulmonary circulation enable thrombopoiesis
Thrombopoiesis is the biological process dedicated to the production of functional platelets by their precursors, megakaryocytes (MKs). During their maturation in the bone marrow (BM), MKs migrate to the vascular niche [1], but the final maturation step that involves the process of platelet release is not fully documented in human physiology [2]. (Source: Experimental Hematology)
Source: Experimental Hematology - April 11, 2018 Category: Hematology Authors: Yasmine Ouzegdouh, Claude Capron, Thomas Bauer, Etienne Puymirat, Jean-Luc Diehl, John F. Martin, Elisabeth Cramer-Bord é Tags: Brief Communication Source Type: research

The physical and cellular conditions of the human pulmonary circulation, enable thrombopoesis#
Thrombopoiesis is the biological process dedicated to the production of functional platelets by their precursors, megakaryocytes (MKs). During their maturation in the bone marrow (BM), MKs migrate to the vascular niche [2] but the final maturation step which involves the process of platelet release is not fully documented in human physiology [1] (Source: Experimental Hematology)
Source: Experimental Hematology - April 11, 2018 Category: Hematology Authors: Yasmine Ouzegdouh, Claude Capro n, Thomas Bauer, Etienne Puymirat, Jean-Luc Diehl, John F . Martin, Elisabeth Cramer-Bord é Source Type: research

Harnessing the potential of epigenetic therapies for childhood acute myeloid leukemia
Acute myeloid leukemia (AML) results from clonal expansion of primitive myeloid cells that are incapable of differentiation. These clones have acquired genetic and epigenetic alterations that cause uncontrolled proliferation at the expense of normal hematopoiesis, leading to bone marrow exhaustion. The recent identification and characterization of many of these alterations [1] create the opportunity for the development of targeted treatments. Cancer genome consortiums have identified genes commonly mutated in AML, many of which are associated with epigenetic regulation [2 –5], indicating that chromatin modifiers play...
Source: Experimental Hematology - March 30, 2018 Category: Hematology Authors: Ashley A. Newcombe, Brenda E.S. Gibson, Karen Keeshan Tags: Review Source Type: research

Harnessing the potential of epigenetic therapies for childhood AML
• Overview of the major epigenetic mutations and mechanisms contributing to paediatric and adult AML• Summary of different clinical trials with epigenetic implications in paediatric and adult AML• Rationale for epigenetic therapies in AML (Source: Experimental Hematology)
Source: Experimental Hematology - March 30, 2018 Category: Hematology Authors: Ashley A. Newcombe, Brenda E.S Gibson, Karen Keeshan Tags: Review Source Type: research

A comparison of intrauterine hemopoietic cell transplantation and lentiviral gene transfer for the correction of severe β-thalassemia in a HbbTh3/+ murine model
The hemoglobinopathies are the most prevalent monogenetic disorders and generate substantial medical and socioeconomic burden worldwide [1]. α-Thalassemia major is perinatally lethal and necessitates effective intrauterine intervention to avoid the complications of chronic severe hypoxia evident in transfusion-dependent survivors [2]. β-Thalassemia major and sickle cell disease (SCD) demand substantial resources to prevent permanent or gan failure [3]. Much of the disease burden arises from suboptimal treatment [4]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 29, 2018 Category: Hematology Authors: Niraja M. Dighe, Kang Wei Tan, Lay Geok Tan, Steven S.W. Shaw, Suzanne M.K. Buckley, Dedy Sandikin, Nuryanti Johana, Yi-Wan Tan, Arijit Biswas, Mahesh Choolani, Simon N. Waddington, Michael N. Antoniou, Jerry K.Y. Chan, Citra N.Z. Mattar Tags: Brief Communication Source Type: research

A comparison of intrauterine haemopoietic cell transplantation and lentiviral gene transfer for the correction of severe β-thalassaemia in a HbbTh3/+ murine model.
• HbbTh3/+ mouse is a good model of severe thalassaemia for in-utero therapy• Better chimerism after in-utero and postnatal transplantation with immunosuppression• In-utero gene therapy produced partial haematological correction but not full rescue• Both strategies need further optimisation to overcome hostile microenvironment (Source: Experimental Hematology)
Source: Experimental Hematology - March 29, 2018 Category: Hematology Authors: Niraja M. Dighe, Kang Wei Tan, Lay Geok Tan, Steven S.W. Shaw, Suzanne M.K. Buckley, Dedy Sandikin, Nuryanti Johana, Yi-Wan Tan, Arijit Biswas, Mahesh Choolani, Simon N. Waddington, Michael N. Antoniou, Jerry K.Y. Chan, Citra N.Z. Mattar Tags: Brief Communication Source Type: research

miR-326 regulates HbF synthesis by targeting EKLF in human erythroid cells
Erythroid Kr üppel-like factor (EKLF), a master regulator of erythropoiesis, plays an important regulatory role in γ- to β-globin gene switching [1–3]. Knockdown of EKLF in human erythroid progenitor cells leads to increased fetal hemoglobin (HbF) expression and murine knockout of Eklf leads to impaired sil encing of transgenic human γ-globin [3–5]. Recent data suggest that haploinsufficiency of EKLF caused by genetic variants is accompanied by significant increases in HbF levels [4,6–8]. Our previous study showed that EKLF mutations ameliorate the clinical severity of β-thalass...
Source: Experimental Hematology - March 27, 2018 Category: Hematology Authors: Yihong Li, Dun Liu, Xinhua Zhang, Zhiming Li, Yuhua Ye, Qifa Liu, Jie Shen, Zhi Chen, Huajie Huang, Yunhao Liang, Xu Han, Jing Liu, Xiuli An, Narla Mohandas, Xiangmin Xu Source Type: research

MicroRNA-155 expression and function in AML: An evolving paradigm
Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that result in dysregulated proliferation. AML represents ~1 –2% of all cancers and occurs more frequently over the age of 60 (incidence of 20 per 100,000) [1]. Acute leukemia is the most common form of pediatric cancer, with AML accounting for ~20% of all leukemias in children. (Source: Experimental Hematology)
Source: Experimental Hematology - March 27, 2018 Category: Hematology Authors: Nisha Narayan, Cameron P. Bracken, Paul G. Ekert Tags: Review Source Type: research

miR-326 regulates HbF synthesis by targeting EKLF in human erythroid cells
• EKLF expression is down-regulated by miR-326 binding to the 3'UTR at the translational level.• miR-326 plays role in hemoglobin switching and erythroid differentiation via EKLF.• miR-326 expression is positively correlated with HbF levels in β-thalassemia major patients. (Source: Experimental Hematology)
Source: Experimental Hematology - March 27, 2018 Category: Hematology Authors: Yihong Li, Dun Liu, Xinhua Zhang, Zhiming Li, Yuhua Ye, Qifa Liu, Jie Shen, Zhi Chen, Huajie Huang, Yunhao Liang, Xu Han, Jing Liu, Xiuli An, Narla Mohandas, Xiangmin Xu Source Type: research

MicroRNA-155 expression and function in AML: an evolving paradigm
• microRNAs are dysregulated in AML.• microRNA expression profiles are useful for disease classification and prognosis.• Expression levels of microRNA-155 influence its function in AML.• microRNA-155 targets transcription factor networks in AML.• Differential regulation of microRNA-155 exp ression in inflammation and cancer. (Source: Experimental Hematology)
Source: Experimental Hematology - March 27, 2018 Category: Hematology Authors: Nisha Narayan, Cameron P. Bracken, Paul G. Ekert Tags: Review Source Type: research

SWI/SNF subunit expression heterogeneity in human aplastic anemia stem/progenitors
Acquired aplastic anemia (AA) represents bone marrow (BM) failure caused by immune-system-mediated destruction of hematopoietic stem cells (HSCs) [1]. Gene expression profiling of AA HSCs suggests the presence of a stressed and immunologically activated target cell population [2]. Next-generation sequencing studies have identified somatic mutations, particularly in BCOR/BCORL1, PIGA, DNMT3A, and ASXL1, in AA patients [3,4]. Clonal hematopoiesis (CH) in AA is associated with evolution to myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) [1]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 26, 2018 Category: Hematology Authors: Sayantani Sinha, Shankha Subhra Chatterjee, Mayukh Biswas, Arijit Nag, Debasis Banerjee, Rajib De, Amitava Sengupta Tags: Brief Communication Source Type: research

SWI/SNF subunit expression heterogeneity in human aplastic anemia stem/progenitors
SWI/SNF Subunit Expression Heterogeneity Associated with Clonal Hematopoiesis. Representation of Differential Expression of SWI/SNF Subunits in Human AA CD34+ Cells. SWI/SNF Expression Remains Unaltered in Myelodysplasia (MDS) (Apart From SMARCD1 Loss) and Aged CD34+ Cells Except ACTL6A, Which is Upregulated in Aged Hematopoietic Stem/Progenitor Cells. Arrows Indicate Up/Downregulated Gene Expression. (Source: Experimental Hematology)
Source: Experimental Hematology - March 26, 2018 Category: Hematology Authors: Sayantani Sinha, Shankha Subhra Chatterjee, Mayukh Biswas, Arijit Nag, Debasis Banerjee, Rajib De, Amitava Sengupta Tags: Brief Communication Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - March 14, 2018 Category: Hematology Source Type: research

Senescent human hematopoietic progenitors show elevated expression of transposable elements and inflammatory genes
Cellular senescence, a state of permanent cell cycle arrest, can be induced by a variety of stressors [1]. Senescence plays a role in tumor suppression and escape from senescence has been identified as a set of cellular processes that can lead to the development of cancer [2]. Approximately 50% of the genome is composed of transposable elements (TEs) [3,4] and we recently characterized the expression of TEs during the development of acute myeloid leukemia (AML), a malignancy considered to arise from hematopoietic stem/progenitor cells (HSPCs) [5]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 13, 2018 Category: Hematology Authors: Stephen Capone, Kwasi M. Connor, Anthony Colombo, Xin Li, Tim J. Triche, Giridharan Ramsingh Tags: Brief Communication Source Type: research

Senescent human hematopoietic progenitors show elevated expression of transposable elements and inflammatory genes
• Senescent human hematopoietic progenitors show increased transposable element expression.• Percentage of circulating hematopoietic progenitors does not increase with age.• Transposable element expression may contribute to immune pathway activation in senescence. (Source: Experimental Hematology)
Source: Experimental Hematology - March 13, 2018 Category: Hematology Authors: Stephen Capone, Kwasi M. Connor, Anthony Colombo, Xin Li, Tim J. Triche, Giridharan Ramsingh Tags: Brief Communication Source Type: research

Analysis of relapse after transplantation in acute leukemia: A comparative on second allogeneic hematopoietic cell transplantation and donor lymphocyte infusions
Relapse of acute leukemia (AL) after allogeneic hematopoietic cell transplantation (Allo-HCT) entails a dismal prognosis and its approach remains challenging. The relapse rate of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) after transplantation vary between 30% and 50%, depending on a wide range of factors such as the transplantation platform [1], disease risk [2], and the intensity of T-cell depletion (TCD) [3], among others. Posttransplantation relapse is associated with poor survival rates [4 –6]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 8, 2018 Category: Hematology Authors: Guillermo Ort í, Jaime Sanz, Irene García-Cadenas, Isabel Sánchez-Ortega, Laura Alonso, Maria José Jiménez, Luisa Sisinni, Carmen Azqueta, Olga Salamero, Isabel Badell, Christelle Ferra, Cristina Diaz de Heredia, Rocio Parody, Miguel Angel Sanz, Jorg Source Type: research

Analysis of relapse post transplant in acute leukemia, a comparative on second allogeneic hematopoietic cell transplant and donor lymphocyte infusions
• In this cohort of AML and ALL patients, second Allo-HCT and DLI showed comparable results.• The time interval from Allo-HCT to relapse is a strong predictor of outcomes for DLI and Second Allo-HCT, a shorter time associated lower OS and DFS.• Within the DLI cohort, patients receiving TCD at Allo-HCT had higher OS, DFS and lower relapse incidence. (Source: Experimental Hematology)
Source: Experimental Hematology - March 8, 2018 Category: Hematology Authors: Guillermo Ort í, Jaime Sanz, Irene García-Cadenas, Isabel Sánchez-Ortega, Laura Alonso, Maria José Jiménez, Luisa Sisinni, Carmen Azqueta, Olga Salamero, Isabel Badell, Christelle Ferra, Cristina Diaz de Heredia, Rocio Parody, Miguel Angel Sanz, Jorg Source Type: research

High-level embryonic globin production with efficient erythroid differentiation from a K562 erythroleukemia cell line
A widely available cell line with erythroid differentiation capability is a useful tool with which to analyze red blood cell (RBC) biology and develop new genetic strategies for RBC diseases. Genetic modification of erythroid progenitor cells and hematopoietic stem cells (HSCs) is potentially curative for hemoglobin disorders, including β-thalassemia and sickle cell disease (SCD). In current gene therapy trials for hemoglobin disorders, a correct β-globin gene is transferred to HSCs and the gene-modified HSCs are transplanted to patients [1,2]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 7, 2018 Category: Hematology Authors: Naoya Uchida, Juan J. Haro-Mora, Selami Demirci, Atsushi Fujita, Lydia Raines, Matthew M. Hsieh, John F. Tisdale Source Type: research

PD-1 deficiency augments bone marrow failure in a minor-histocompatibility antigen mismatch lymphocyte infusion model
Since the first clinical trial of the anti-PD-1 agent nivolumab in 2010 [1], PD-1 blockade has revolutionized the field of cancer immunotherapy. Despite the successes of PD-1-blocking agents in cancer treatment, a major and often life-threatening complication of their use is the development of immune-related adverse events (irAEs). The incidence of all irAEs in nivolumab-treated patients ranges from 30% to 45% and more severe grade 3 –4 irAEs occur in 3–7% of patients [2]. Most common are diarrhea/colitis, pruritis, hepatitis, and hypophysitis [3], but a number of relatively rare autoimmune diseases, such as my...
Source: Experimental Hematology - March 7, 2018 Category: Hematology Authors: Maile K. Hollinger, Valentina Giudice, Nicole A. Cummings, Guillermo Rivell, Hansheng Zhang, Sachiko Kajigaya, Keyvan Keyvanfar, Jichun Chen, Xingmin Feng, Neal S. Young Source Type: research

High-level embryonic globin production with efficient erythroid differentiation from a k562 erythroleukemia cell line
In this study, we sought to improve erythroid differentiation from K562 cells to enable protein-level globin analysis. K562 cells were exposed to a variety of reagents including hemin, rapamycin, imatinib, and/or decitabine (known erythroid inducers), and cultured in basic culture media or erythropoietin-based differentiation media. (Source: Experimental Hematology)
Source: Experimental Hematology - March 7, 2018 Category: Hematology Authors: Naoya Uchida, Juan J. Haro-Mora, Selami Demirci, Atsushi Fujita, Lydia Raines, Matthew M. Hsieh, John F. Tisdale Source Type: research

PD-1 deficiency augments bone marrow failure in a minor-histocompatibility antigen mismatch lymphocyte infusion model
Authorship Statement (Source: Experimental Hematology)
Source: Experimental Hematology - March 7, 2018 Category: Hematology Authors: Maile K. Hollinger, Valentina Giudice, Nicole A. Cummings, Guillermo Rivell, Hansheng Zhang, Sachiko Kajigaya, Keyvan Keyvanfar, Jichun Chen, Xingmin Feng, Neal S. Young Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - March 1, 2018 Category: Hematology Source Type: research

Megakaryocyte ontogeny: Clinical and molecular significance
Megakaryocytes (Mks) are specialized mammalian marrow cells responsible for platelet production. They arise from bipotent megakaryocyte-erythroid progenitors [1]. Their differentiation includes a unique program of endomitosis that drives nuclear polyploidization and cellular enlargement. This process is accompanied by lineage consolidation involving downregulation of erythroid genes and upregulation of Mk surface markers, as well as development of cytoplasmic granules, multivesicular bodies, and demarcation membranes. (Source: Experimental Hematology)
Source: Experimental Hematology - February 28, 2018 Category: Hematology Authors: Kamaleldin E. Elagib, Ashton T. Brock, Adam N. Goldfarb Tags: Review Source Type: research

New genetic tools for the in vivo study of hematopoietic stem cell function
Adult hematopoietic stem cells (HSCs) have the ability to both self-renew and differentiate, reconstituting a majority of the lineages of the hematopoietic system and ensuring lifelong hematopoiesis. These properties are essential for the success of bone marrow (BM) transplantations both in the clinical setting and in the laboratory. Over the years, numerous challenges have impeded the study of HSCs, including their paucity in the BM and differences in the definition of an HSC at the phenotypic level as assessed by cell surface markers and at the functional level as measured by transplantation assays [1 –7]. (Source:...
Source: Experimental Hematology - February 28, 2018 Category: Hematology Authors: Samik Upadhaya, Boris Reizis, Catherine M. Sawai Tags: Review Source Type: research

Megakaryocyte ontogeny: clinical and molecular significance
• Fetal Mk are phenotypically different than adult Mk• Fetal Mk are matured as adult Mk• Fetal Mk phenotypic features predispose to certain Mk related diseases• Cell intrinsic and extrinsic factors contribute to Mk ontogenic differences• Fetal Mk can be established in adult mode to enhance ex vivo platelets production (Source: Experimental Hematology)
Source: Experimental Hematology - February 28, 2018 Category: Hematology Authors: Kamaleldin E. Elagib, Ashton T. Brock, Adam N. Goldfarb Tags: Review Source Type: research

New genetic tools for the in vivo study of hematopoietic stem cell function
• Genetic reporter systems enable prospective identification of bona fide hematopoietic stem cells (HSCs)• Most adult HSCs make a major contribution to steady state hematopoiesis• Minor fraction of stable label-retaining HSCs persists even with age• New roles for mitochondria and metabolic s tate in regulating HSC function in vivo (Source: Experimental Hematology)
Source: Experimental Hematology - February 28, 2018 Category: Hematology Authors: Samik Upadhaya, Boris Reizis, Catherine M. Sawai Tags: Review Source Type: research

Deficiency in the DNA glycosylases UNG1 and OGG1 does not potentiate c-Myc-induced B-cell lymphomagenesis
Lymphomas are a group of cancers that occur in lymphoid tissue during lymphocyte development. The majority of lymphomas (95%) are of B-cell origin [1], and despite the extensive research focusing on understanding the molecular events leading to this disease, the full mechanistic details remain elusive. It is now accepted that the natural processes guiding normal B-cell activation and differentiation are at the root of B-cell transformation. B cells are highly susceptible to chromosomal translocations, mainly due to the fact that the process of antibody diversification involves naturally induced DNA breaks and mutations [2]...
Source: Experimental Hematology - February 26, 2018 Category: Hematology Authors: Blerta Green, Alberto Martin, Antoaneta Belcheva Source Type: research

Deficiency in the DNA glycosylases UNG1 and OGG1 does not potentiate c-myc-induced B-cell lymphomagenesis
C-Myc overexpression mediates lymphomagenesis, however, secondary genetic lesions are required for its full oncogenic potential. The origin and the mechanism of formation of these mutations are unclear. Using the lacI-mutation detection system, we show that secondary mutations occur early in B-cell development and are repaired by Msh2. The mutations at the lacI gene were predominantly at C:G base pairs and CpG motifs suggesting that they were formed due to cytosine deamination or oxidative damage of G. (Source: Experimental Hematology)
Source: Experimental Hematology - February 26, 2018 Category: Hematology Authors: Blerta Green, Alberto Martin, Antoaneta Belcheva Source Type: research

Venetoclax: A new wave in hematooncology
Eukaryotic cells can die in many ways, including physiological and mostly beneficial modes of death (e.g., apoptosis, necroptosis, and pyroptosis), as well as nonphysiological and harmful necrotic cell destruction [1]. The classical form of cell death, apoptosis, is a gene-directed process of cell suicide characterized by specific biochemical and morphological changes including activation of proteolytic enzymes, caspases, cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. (Source: Experimental Hematology)
Source: Experimental Hematology - February 22, 2018 Category: Hematology Authors: Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek Tags: Review Source Type: research

The BMP pathway: A unique tool to decode the origin and progression of leukemia
During embryogenesis and development, the fate of stem cells (SCs) is guided by intrinsic and environmental cues, such as surrounding cells, matrix, and soluble factors. During cancer development, the maintenance and evolution of cancer stem cells (CSCs) also depends on their microenvironment. This has been particularly demonstrated in the hematological field, where the differentiation hierarchy from hematopoietic stem cells (HSCs) is a model and in which the existence of CSCs was first shown [1 –4]. (Source: Experimental Hematology)
Source: Experimental Hematology - February 22, 2018 Category: Hematology Authors: Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, V éronique Maguer-Satta Tags: Review Source Type: research

Venetoclax: a new wave in hematooncology
Eukaryotic cells can die in many ways, including physiological and mostly beneficial modes of death (e.g., apoptosis, necroptosis, and pyroptosis), as well as nonphysiological and harmful necrotic cell destruction [1]. The classical form of cell death, apoptosis, is a gene-directed process of cell suicide characterized by specific biochemical and morphological changes including activation of proteolytic enzymes, caspases, cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. (Source: Experimental Hematology)
Source: Experimental Hematology - February 22, 2018 Category: Hematology Authors: Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek Tags: Review Source Type: research