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Venetoclax: a new wave in haemato-oncology
• Cancer cells survive via overexpressed anti-apoptotic BCL2 proteins• Venetoclax is highly selective BCL2 inhibitor with acceptable toxicity profile• It overcomes resistance to ibrutinib and idelalisib in chronic lymphocytic leukemia• Effective in a subset of multiple myeloma with high with t(11;14)• Synergic activity with low-dose cytarabine, 5-azacytidine in acute myeloid leukemia (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 origin and progression of leukemia
During embryogenesis and development, stem cell (SC) fates are 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 (CSC) also depends on their microenvironment. This has been particularly demonstrated in the hematological field where the differentiation hierarchy from Hematopoietic stem cells (HSC) is a model and in which the existence of CSC was first shown1-4. Among soluble molecules involved in SC fate, Bone Morphogenetic Proteins (BMPs) have been shown to both regulate self-renewal and differentiat...
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 Source Type: research

A regulatory circuitry between miR-193a/miR-600 and WT1 enhances leukemogenesis in acute myeloid leukemia
MicroRNAs, which inhibit target gene expression through mainly binding 3'-untranslated regions (3'UTR) or seldom binding coding sequence (CDS) of target gene mRNA, are class of small non-coding RNAs[1]. MiRNAs modulate several important biological processes, such as apoptosis, cell cycle, proliferation, differentiation, and epigenetic changes[2, 3]. Single miRNA probably regulates hundreds of target genes and one single gene might be regulated by several miRNAs. Thus, miRNA-mRNA regulatory net plays an important role in diverse biological processes. (Source: Experimental Hematology)
Source: Experimental Hematology - February 13, 2018 Category: Hematology Authors: Haiying Li, Chongyun Xing, Bin Zhou, Haige Ye, Jianhua Feng, Jianbo Wu, Shenmeng Gao Source Type: research

High-throughput single-cell fate potential assay of murine hematopoietic progenitors in vitro
Recent single-cell transcriptomic studies have led to the proposal of new models for the hematopoietic hierarchy [1 –10]. Testing these models requires matching cell transcriptional state with functional cell fate potential at the single-cell level. Older studies have reported “low-throughput” single-cell differentiation assays in vitro, where outcome is measured using colony formation and morphological cri teria [11–13]. Recently, tracking of single hematopoietic stem cell differentiation by in vitro imaging has also been described [14,15], and index sorting was used to link single-cell transcripto...
Source: Experimental Hematology - February 3, 2018 Category: Hematology Authors: Betsabeh Khoramian Tusi, Merav Socolovsky Tags: Methods and Techniques Source Type: research

High throughput single-cell fate potential assay of murine hematopoietic progenitors in vitro
The advent of single cell transcriptomics has led to the proposal of a number of novel high- resolution models for the hematopoietic system. Testing the predictions generated by such models requires cell fate potential assays of matching, single cell resolution. Here we detail the development of an in vitro high throughput single-cell culture assay using flow-cytometrically-sorted single murine bone-marrow progenitors, that measures their differentiation into any of 5 myeloid lineages. We identify critical parameters for single cell culture outcome, including the choice of sorter nozzle size and pressure, culture media and...
Source: Experimental Hematology - February 3, 2018 Category: Hematology Authors: Betsabeh Khoramian Tusi, Merav Socolovsky Tags: Methods and Techniques Source Type: research

Engineered humanized bone organs maintain human hematopoiesis in vivo
• Human MSCs-derived ossicles can support multi-lineage human hematopoiesis• Functional human HSPCs are maintained in the human ossicle• Human HSCs cycle less in human ossicles than in mouse bone marrow (Source: Experimental Hematology)
Source: Experimental Hematology - February 2, 2018 Category: Hematology Authors: Kristin Fritsch, S ébastien Pigeot, Xiaomin Feng, Paul E. Bourgine, Timm Schroeder, Ivan Martin, Markus G. Manz, Hitoshi Takizawa Tags: Brief Communications Source Type: research

Tumor suppressor BTG1 limits activation of BCL6 expression downstream of ETV6-RUNX1
• Loss of BTG1 potentiates ETV6-RUNX1-mediated self-renewal capacity• Tumor suppressor BTG1 limits activation of BCL6 by ETV6-RUNX1• BCL6 enhances the clonogenicity of primitive B lymphoid progenitors (Source: Experimental Hematology)
Source: Experimental Hematology - February 2, 2018 Category: Hematology Authors: Esther Tijchon, Liesbeth van Emst, Laurensia Yuniati, Dorette van Ingen Schenau, Myl ène Gerritsen, Laurens T. van der Meer, Owen Williams, Peter M. Hoogerbrugge, Blanca Scheijen, Frank N. van Leeuwen Tags: Brief Communications Source Type: research

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

Remembering Ihor Lemischka —The Scientist's Scientist
On December 7, 2017, we were saddened to learn of the untimely death of Ihor Lemischka, one of the giants of modern biomedicine. Always uncompromising in his thinking, often unadulterated in his remarks, and frequently brilliant in his approach to problems, Ihor was the scientist's scientist. He was, indeed, the epitome of focus and intellectualism. Some may remember his sometimes gruff and impatient exterior, but those who knew Ihor well understood that he had a truly good heart and a rare strength of spirit. (Source: Experimental Hematology)
Source: Experimental Hematology - January 17, 2018 Category: Hematology Authors: Anna Rita Migliaccio, Ronald Hoffman Source Type: research

BTLA marks a less cytotoxic T-cell subset in diffuse large B-cell lymphoma with high expression of checkpoints
The immune system plays an important role in the development of cancer [1,2], including hematologic malignancies [3]. PD-1 is highly expressed in the microenvironment of hematologic malignancies, such as diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and classic Hodgkin lymphoma (cHL) [4 –6]. Cancer immunotherapy via immune checkpoint blockade, especially PD-1 blockade, has shown encouraging results in many clinical trials in DLBCL and cHL [7,8]. Recently, combinations of PD-1 blockade with other checkpoint inhibitors, such as CTLA-4, BTLA, TIM-3, LIGHT, and LAG-3, have emerged as a novel direction ...
Source: Experimental Hematology - January 15, 2018 Category: Hematology Authors: Lina Quan, Xiuwen Lan, Yuanyuan Meng, Xiuchen Guo, Yiwei Guo, Lina Zhao, Xue Chen, Aichun Liu Source Type: research

BTLA marks a less cytotoxic T-cell subset in diffuse large B-cell lymphoma with high-expression of checkpoints
We reported the high expression of BTLA in micro-environment of DLBCL• The cyto-toxicity and differentiation of BTLA+ T-cells were analyzed in this report.• BTLA high expression has correlation with advanced stage of DLBCL.• Our data provides the first evidence that increased BTLA predicts poor prognosis in patients with DLBCL.• Our results hint to the blockade of BTLA may represent a new strategy for DLBCL. (Source: Experimental Hematology)
Source: Experimental Hematology - January 15, 2018 Category: Hematology Authors: Lina Quan, Xiuwen Lan, Yuanyuan Meng, Xiuchen Guo, Yiwei Guo, Lina Zhao, Xue Chen, Aichun Liu Source Type: research

Blockade of placental growth factor reduces vaso-occlusive complications in murine models of sickle cell disease
Sickle cell disease (SCD) is the most frequent hemoglobinopathy among the common inherited hematologic disorders in the world [1]. It is a genetic disorder caused by a single amino acid substitution in the beta globin gene, from glutamic acid to valine (E6V) [2]. When sickle hemoglobin is deoxygenated, it polymerizes via hydrophobic interactions introduced by the mutant valine [3]. As a result, red blood cells (RBCs) form a sickle shape, their deformability decreases, and their adhesiveness to the vascular endothelial cells and white blood cells increases [4-7]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 11, 2018 Category: Hematology Authors: Jian-Ming Gu, Shujun Yuan, Derek Sim, Keith Abe, Perry Liu, Martin Rosenbruch, Peter Bringmann, Katalin Kauser Source Type: research

Phenotypic and molecular characterization of a serum-free miniature erythroid differentiation system suitable for high-throughput screening and single-cell assays
In vitro erythroid differentiation systems are essential tools for understanding normal and abnormal human erythropoiesis and for testing extracellular factors affecting erythropoiesis. A number of techniques have been described for the production of erythroblasts in cultures, many of which require stromal cell support [1]. Since the initial description [2], several liquid culture systems that do not require supporting stroma have been introduced [3]. Most of these utilize animal serum or conditioned medium with variable composition affecting the consistency and reproducibility of such assays [4,5]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 9, 2018 Category: Hematology Authors: Sachith Mettananda, Kevin Clark, Chris A. Fisher, Jackie A. Sloane-Stanley, Richard J. Gibbons, Douglas R. Higgs Source Type: research

Phenotypic and molecular characterisation of a serum-free miniature erythroid differentiation system suitable for high throughput screening and single cell assays
• Miniature erythroid culture generates large number of pure and synchronous erythroid cells• This system morphologically and immunology recapitulates in vivo erythropoiesis• This was validated to assess changes in globin gene expression• Terminal erythroid cells were generated by single hae matopoietic stem cells (Source: Experimental Hematology)
Source: Experimental Hematology - January 9, 2018 Category: Hematology Authors: Sachith Mettananda, Kevin Clark, Chris A. Fisher, Jackie A. Sloane-Stanley, Richard J. Gibbons, Douglas R. Higgs Source Type: research

Megakaryocyte-derived excessive transforming growth factor β1 inhibits proliferation of normal hematopoietic stem cells in acute myeloid leukemia
Acute myeloid leukemia (AML) is characterized by excessive proliferation of immature myeloid precursors and impaired production of healthy hematopoietic cells, which cause high morbidity and mortality [1 –4]. Previous studies have revealed the growth arrest and differentiation blockade of normal hematopoietic stem and progenitor cells (HSPCs) in acute leukemia hosts [5,6]. Several intrinsic factors, such as Hes1, p21, and Egr3, have been identified to be responsible for the deep quiescence of norm al HSPCs in leukemia [6,7]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 4, 2018 Category: Hematology Authors: Yuemin Gong, Mei Zhao, Wanzhu Yang, Ai Gao, Xiuxiu Yin, Linping Hu, Xiaofang Wang, Jing Xu, Sha Hao, Tao Cheng, Hui Cheng Tags: Brief Communications Source Type: research

Megakaryocyte-derived excessive TGF β1 inhibits proliferation of normal hematopoietic stem cells in acute myeloid leukemia
• TGFβ signaling pathway was activated in residual hematopoietic stem cells in AML bone marrow.• Megakaryocytes produced excessive TGFβ1 in leukemic bone marrow.• TGFβ1 directly up-regulated Egr3 in hematopoietic stem cells. (Source: Experimental Hematology)
Source: Experimental Hematology - January 4, 2018 Category: Hematology Authors: Yuemin Gong, Mei Zhao, Wanzhu Yang, Ai Gao, Xiuxiu Yin, Linping Hu, Xiaofang Wang, Jing Xu, Sha Hao, Tao Cheng, Hui Cheng Tags: Brief Communications Source Type: research

High fat diet-induced obesity exacerbates hematopoiesis deficiency and cytopenia caused by 5-fluorouracil via peroxisome proliferator-activated receptor γ
Obesity is associated with premature death and reduced quality of life [1,2]. It has been considered an important risk factor for many pathological conditions including diabetes, atherosclerosis, and skeletal system disease [3,4]. Changes in the function of the hematopoietic and immune cell compartments are an attractive concept to explain the deleterious effects of obesity on organisms. Although emerging evidence indicates that high fat diet-induced obesity changes the bone marrow microenvironment [5], leading to alterations in the development of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and multiple...
Source: Experimental Hematology - January 3, 2018 Category: Hematology Authors: Yanhong Li, Shuai Zhu, Yuanyuan Zhang, Ting Liu, Linchong Su, Qiuping Zhang, Yubin Luo Source Type: research

High fat diet induced obesityexacerbateshematopoiesis deficiency and cytopenia caused by 5-fluorouracil via PPAR- γ
• HFD exacerbates 5- Fluouracil-induced myelosuppresseion and cytopenia• HFD impacts platelet proliferation by regulating Vcam-1/Vla-4 signal pathway in BM• BADGE treatment alleviates aggravated hematopoiesis and cytopenia under HFD (Source: Experimental Hematology)
Source: Experimental Hematology - January 3, 2018 Category: Hematology Authors: Yanhong Li, Shuai Zhu, Yuanyuan Zhang, Ting Liu, Linchong Su, Qiuping Zhang, Yubin Luo Source Type: research

Scriptaid inhibits cell survival, cell cycle, and promotes apoptosis in multiple myeloma via epigenetic regulation of p21
Multiple myeloma (MM) is malignant hematological disease that leads to approximately 80,000 deaths every year [1]. Many novel therapeutic approaches, including hematopoietic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, have led to dramatically improved survival for MM patients [2,3]. However, MM remains an incurable disease and its molecular mechanisms require further study. (Source: Experimental Hematology)
Source: Experimental Hematology - January 2, 2018 Category: Hematology Authors: Ruosi Yao, Danyang Han, Xiaoyang Sun, Yu Xie, Qingyun Wu, Chunling Fu, Yao Yao, Hujun Li, Zhenyu Li, Kailin Xu Source Type: research

Scriptaid inhibits cell survival, cell cycle and promotes apoptosis in multiple myeloma via epigenetic regulation of p21
• HDAC inhibitor Scriptaid inhibits MM cell proliferation and cell cycle.• Scriptaid induces MM cell apoptosis.• p21 is the key regulator of Scriptaid-mediated cell death.• Scriptaid activates p21 transcription by increasing H3Ac level at its promoter. (Source: Experimental Hematology)
Source: Experimental Hematology - January 2, 2018 Category: Hematology Authors: Ruosi Yao, Danyang Han, Xiaoyang Sun, Yu Xie, Qingyun Wu, Chunling Fu, Yao Yao, Hujun Li, Zhenyu Li, Kailin Xu Source Type: research

The mirn23a and mirn23b MicroRNA clusters are necessary for proper hematopoietic progenitor cell production and differentiation
• Mirn23a/Mirn23b deficient mice exhibit decreased HSPCs and bone marrow cellularity• Loss of mirn23a/mirn23b in HSPC populations results in increased apoptosis• Mirn23a/mirn23b loss skews hematopoietic differentiation towards the B cell lineage• Mirn23a/mirn23b loss alters hematopoietic and apoptotic gene expression pathways (Source: Experimental Hematology)
Source: Experimental Hematology - December 27, 2017 Category: Hematology Authors: Jeffrey L. Kurkewich, Austin Boucher, Nathan Klopfenstein, Ramdas Baskar, Reuben Kapur, Richard Dahl Source Type: research

Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors
• DEK loss causes restricted HPCs to enter quiescence (G0) in response to radiation• DEK's role in radiation response is functionally unique in HPC1 progenitors vs HPC2• DEK loss causes aberrant radioresistance during early myeloid reconstitution (Source: Experimental Hematology)
Source: Experimental Hematology - December 27, 2017 Category: Hematology Authors: J. Serrano-Lopez, K. Nattamai, N.A. Pease, M.S. Shephard, A.M. Wellendorf, M. Sertorio, E.A. Smith, H. Geiger, S.I. Wells, J.A. Cancelas, L.M. Privette Vinnedge Source Type: research

Many layers of embryonic hematopoiesis: new insights into B-cell ontogeny and the origin of hematopoietic stem cells
Functionally defined, hematopoietic stem cells (HSCs) have the unique ability to reconstitute the entire hematopoietic program of a conditioned adult recipient, which implies the capacity for homing and engraftment in the bone marrow niche, for life-long self-renewal, and for multilineage hematopoietic differentiation. During embryonic development, HSCs arise from specialized hemogenic endothelium residing in arterial blood vessels in a process referred to as the endothelial to hematopoietic transition (EHT) [1] before they undergo further maturation and expansion in the liver during the fetal period and finally home to th...
Source: Experimental Hematology - December 26, 2017 Category: Hematology Authors: Brandon Kenneth Hadland, Momoko Yoshimoto Source Type: research

Phosphoinositide-dependent protein kinase 1 is a potential novel therapeutic target in mantle cell lymphoma
• PDPK1 is found to be constitutively activated in various types of patient-derived B-cell NHL cells, including mantle cell lymphoma (MCL) which remains to be a highly treatment refractory disease subtype.• PDPK1 plays pivotal roles in cell survival and proliferation of tumor cells of MCL-derive d cell lines.• PDPK1 is suggested to be a potential therapeutic target in MCL. (Source: Experimental Hematology)
Source: Experimental Hematology - December 26, 2017 Category: Hematology Authors: Saori Maegawa, Yoshiaki Chinen, Yuji Shimura, Kazuna Tanba, Tomoko Takimoto, Yoshimi Mizuno, Yayoi Matsumura-Kimoto, Saeko Kuwahara-Ota, Taku Tsukamoto, Tsutomu Kobayashi, Shigeo Horiike, Masafumi Taniwaki, Junya Kuroda Source Type: research

Many layers of embryonic hematopoiesis: new insights into B cell ontogeny and the origin of hematopoietic stem cells
• During embryonic development, initial hematopoietic progenitors are generated from hemogenic endothelium in multiple waves independently of HSC.• Recent studies highlight the contribution of embryonic waves of HSC-independent hematopoiesis to unique innate-like immune cells that can persist as self-maintaining hematopoietic populations in adult tissues.• Recent studies suggest that distinct waves of hemogenic endothelium/HSC precursors may contribute to the production of heterogeneous populations of HSC in the fetal liver with distinct self-renewal properties and B cell lineage potenti als. (Source: Experimental Hematology)
Source: Experimental Hematology - December 26, 2017 Category: Hematology Authors: Brandon Hadland, Momoko Yoshimoto Source Type: research

Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, non-peptidyl small-molecule agonist of human thrombopoietin receptor, c-mpl
Thrombocytopenia results from a decrease in platelets due to either increased platelet destruction and/or inadequate platelet production. This is a common problem in the management of patients with cancer and other conditions that affect hematopoietic cells including myelodysplastic syndrome, idiopathic thrombocytopenic purpura (ITP), chronic liver disease, and acquired immunodeficiency syndrome [1-7]. Thrombopoietin (TPO) increases platelet production through stimulation of proliferation and differentiation of megakaryocytic progenitor cells and induction of megakaryocyte maturation [8]. (Source: Experimental Hematology)
Source: Experimental Hematology - December 20, 2017 Category: Hematology Authors: Hiroshi Yoshida, Hajime Yamada, Wataru Nogami, Keiji Dohi, Tomomi Kurino-Yamada, Koji Sugiyama, Koji Takahashi, Yoshinari Gahara, Motoji Kitaura, Minoru Hasegawa, Itsuki Oshima, Kenji Kuwabara Source Type: research

Acute myeloid leukemia xenograft success prediction: saving time
• Extracellular,phenotype, apoptosis or cell cycle profile at thawing cannot predict AML xenograft potential.• Leukemic-LTC-Initiating Cells content distinguish fast or delayed engraftment potential.• Here we define a 1-week CFSE-based assay which predict AML xenograft success. (Source: Experimental Hematology)
Source: Experimental Hematology - December 15, 2017 Category: Hematology Authors: Emmanuel Griessinger, Jacques Vargaftig, Stuart Horswell, David C. Taussig, John Gribben, Dominique Bonnet Tags: Brief Communications Source Type: research

Hematopoietic development: a gap in our understanding of inherited bone marrow failure
Inherited bone marrow failure syndromes (IBMFSs) are multisystem disorders with a predilection for exhaustion of the hematopoietic stem cell (HSC) pool as a near-uniform feature [1,2]. In most patients, symptomatic cytopenias do not manifest until early childhood, but cases of fetal anemia leading to intrauterine hydrops have been reported. Some infants come to attention with constitutional anomalies in other organ systems or through the diagnosis of symptomatic siblings. These seemingly disparate observations are consistent with prenatal HSC defects, even though until recently, few studies had directly pursued this possib...
Source: Experimental Hematology - December 14, 2017 Category: Hematology Authors: Peter Kurre Tags: Perspective Source Type: research

Hematopoietic development - a gap in our understanding of inherited bone marrow failure
• Inherited bone marrow failure syndromes (IBMFS) reveal distinct hematopoietic defects during development• Murine, zebrafish and iPSC models have been used to map in utero onset and pathophysiology (Source: Experimental Hematology)
Source: Experimental Hematology - December 14, 2017 Category: Hematology Authors: Peter Kurre Tags: Perspective Source Type: research

A vicious interplay between genetic and environmental insults in the etiology of blood cancers
• Epigenetic (embryos) and genetic (aging) mechanisms generate multiple HSC clones• Aging reduces the number of active HSC clones• Old HSC clones have lower self-renewal and skewed myeloid differentiation potential• Environmental and genetic insults can cooperately initiate blood cancer• E nvironmental insults may provide proliferative advantages to malignant HSCs (Source: Experimental Hematology)
Source: Experimental Hematology - December 14, 2017 Category: Hematology Authors: Anna Rita Migliaccio Tags: Perspective Source Type: research

57R2A, a newly established monoclonal antibody against mouse GPR56, marks long-term repopulating hematopoietic stem cells
• 57R2A, a novel monoclonal antibody against mouse GPR56, was established.• Flow cytometry using 57R2A demonstrated GPR56 expression in mouse HSC fraction.• 57R2A marked long-term repopulating cells in mouse BMMNCs.• Long-term repopulating potency was consistent with the expression of GPR56 and MPL.• Findings for 57R2A suggest that GPR56 is a positive marker for mouse HSCs. (Source: Experimental Hematology)
Source: Experimental Hematology - December 7, 2017 Category: Hematology Authors: Yusuke Tokoro, Yoko Yamada, Shin-ichiro Takayanagi, Tetsuya Hagiwara Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - December 2, 2017 Category: Hematology Source Type: research

An inflammatory environment containing TNF α favors Tet2-mutant clonal hematopoiesis
• Inactivating TET2 mutations are common drivers of clonal hematopoiesis with aging• TNFα is increased in myelodysplastic syndromes and unhealthy aging• Loss of Tet2 increases murine bone marrow colony formation in the presence of TNFα• Human TET2-mutant bone marrow is resistant to colony- suppressive effects of TNFα• TET2-mutant clones may have greater fitness in an inflammatory environment of aging (Source: Experimental Hematology)
Source: Experimental Hematology - November 28, 2017 Category: Hematology Authors: Samuel O. Abegunde, Rena Buckstein, Richard A. Wells, Michael J. Rauh Tags: Brief Communications Source Type: research

Mechanisms underlying the heterogeneity of myelodysplastic syndromes
• In myelodysplastic syndromes, the disease-initiating cell is a rare hematopoietic stem cell which transmits the genetic abnormalities to its myeloid and lymphoid progeny.• The heterogeneity of MDS phenotypes is related to the diversity of genetic, the various combinations and order of mutation s in cooperating genes, and the variegation of clonal hematopoietic hierarchy.• A mutation in granulo-monocytic progenitor may the transformation into acute myeloid leukemia. (Source: Experimental Hematology)
Source: Experimental Hematology - November 22, 2017 Category: Hematology Authors: Charles Dussiau, Michaela Fontenay Tags: Review Source Type: research

miR-223 is repressed and correlates with inferior clinical features in mantle cell lymphoma through targeting SOX11
MicroRNAs (miRs) are a class of noncoding single-stranded RNA molecules of 21 –23 nucleotides, which bind to 3′-untranslated region (UTR) of the target messenger RNA (mRNA) and trigger either mRNA degradation or inhibition of translation depending on the degree of complementarity between miR and its target [1]. Since the first description of the loss of miR-15/16 in chron ic lymphocytic leukemia (CLL) [2], studies have reported the deregulation of miRs in a variety of hematopoietic and solid tumors, functioning as either oncogenes or tumor suppressors regarding context and cell types [3–5]. (Source: Experimental Hematology)
Source: Experimental Hematology - November 20, 2017 Category: Hematology Authors: Keshu Zhou, Xiaoyan Feng, Yanying Wang, Yanyan Liu, Long Tian, Wenli Zuo, Shuhua Yi, Xudong Wei, Yongping Song, Lugui Qiu Tags: Review Source Type: research

MiRNA-223 functions as both prognostic biomarker and tumor suppressor in mantle cell lymphoma through targeting SOX11
• MiRNA-223 is repressed and predicts a poorer clinical outcome in MCL patients.• MiRNA-223 suppresses cell proliferation and induces apoptosis of MCL cells.• MiRNA-223 is a repressor of SOX11, targeting the regulatory miRNA-223/SOX11 interaction. (Source: Experimental Hematology)
Source: Experimental Hematology - November 20, 2017 Category: Hematology Authors: Keshu Zhou, Xiaoyan Feng, Yanying Wang, Yanyan Liu, Long Tian, Wenli Zuo, Shuhua Yi, Xudong Wei, Yongping Song, Lugui Qiu Tags: Review Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - November 16, 2017 Category: Hematology Source Type: research

T-cell-replete haploidentical transplantation in acute myeloid leukemia
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for patients with acute myeloid leukemia (AML), donor availability within a correct timeframe from the acquisition of cytogenetic or molecular characteristics remains a problem. The probability of finding such a donor is 25%, 75%, 46%, and 16% when looking for an HLA-identical (HLAid) sibling or an HLA-matched unrelated donor (MUD) based on high-resolution HLA typing in Caucasians, patients with Middle Eastern or North African origins, and in African Americans, respectively [1]. (Source: Experimental Hematology)
Source: Experimental Hematology - November 16, 2017 Category: Hematology Authors: Luca Castagna, Raynier Devillier, Norbert Vey, Didier Blaise Source Type: research

T cell replete-haploidentical transplantation in acute myeloid leukemia
• Outcome after Haplo-HSCT for AML is similar to the one using HLA-id donors.• CR1 intermediate risk AML patients lacking HLA-id donor can benefit from haplo-HSCT.• Haplo-HSCT using post transplantation cyclophosphamide provides low incidence of GVHD.• Haplo-HSCT may challenge unrelated dono r transplantation, especially in elderly patients.• Haplo-HSCT is a valuable option for patients with refractory AML. (Source: Experimental Hematology)
Source: Experimental Hematology - November 16, 2017 Category: Hematology Authors: Luca Castagna, Raynier Devillier, Norbert Vey, Didier Blaise Source Type: research

A thalidomide –hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes
Fetal hemoglobin (HbF) induction by hydroxyurea (HU) therapy is associated with decreased morbidity and mortality in sickle cell anemia (SCA) patients, but not all patients respond to or tolerate HU. This provides a rationale for developing novel HbF inducers to treat SCA. Thalidomide analogs have the ability to induce HbF production while inhibiting the release of tumor necrosis factor-alpha. Molecular hybridization of HU and thalidomide was used to synthesize 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C). (Source: Experimental Hematology)
Source: Experimental Hematology - November 3, 2017 Category: Hematology Authors: Carolina Lanaro, Carla Franco-Penteado, Fabio H. Silva, Kleber Y. Fertrin, Jean Leandro dos Santos, Marlene Wade, Shobha Yerigenahally, Thais R. de Melo, Chung Man Chin, Abdullah Kutlar, Steffen E. Meiler, Fernando Ferreira Costa Tags: Brief Communications Source Type: research

A thalidomide-hydroxyurea hybrid increases HbF production in sickle cell mice and reduces the release of proinflammatory cytokines in cultured monocytes
• Compound 4C is a novel hydroxyurea-thalidomide hybrid designed to treat SCA.• Fetal hemoglobin production increased in sickle cell mice treated with compound 4C.• Production of proinflammatory cytokines by monocytes was reduced by compound 4C. (Source: Experimental Hematology)
Source: Experimental Hematology - November 3, 2017 Category: Hematology Authors: Carolina Lanaro, Carla Franco-Penteado, Fabio H. Silva, Kleber Y. Fertrin, Jean Leandro dos Santos, Marlene Wade, Shobha Yerigenahally, Thais R. de Melo, Chung Man Chin, Abdullah Kutlar, Steffen E. Meiler, Fernando Ferreira Costa Tags: Brief Communications Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - November 1, 2017 Category: Hematology Source Type: research

Megakaryocyte and polyploidization
- MK endomitosis associates both a defect in cytokinesis and karyokinesis- A myosin II accumulation defect at the furrow induces the cytokinesis failure- MK polyploidization and maturation have close transcriptional regulation- MK ploidization is functionnally important for efficient platelet production- MK ploidy is altered in many pathologies, but associated with maturation defects (Source: Experimental Hematology)
Source: Experimental Hematology - October 27, 2017 Category: Hematology Authors: Stefania Mazzi, Larissa Lordier, Najet Debili, Hana Raslova, William Vainchenker Tags: Review Source Type: research

KDM6 and KDM4 histone lysine demethylases emerge as molecular therapeutic targets in human acute myeloid leukemia
Dysregulated function in chromatin modifying enzymes remains an important hallmark in acute myeloid leukemia (AML) pathogenesis (1). Growing bodies of evidences highlight involvement of histone demethylases in tumorigenesis (2, 3). Kdm1a, an H3K4Me2/1 and H3K9Me2/1 demethylase was demonstrated to sustain oncogenic potential of MLL-AF9-expressing leukemia stem cells (LSCs) (4). Kdm5b, another H3K4Me3/2 demethylase has been suggested as a tumor suppressor in MLL-rearranged leukemia, inversely affecting LSC function (5). (Source: Experimental Hematology)
Source: Experimental Hematology - October 27, 2017 Category: Hematology Authors: Liberalis Debraj Boila, Shankha Subhra Chatterjee, Debasis Banerjee, Amitava Sengupta Tags: Brief Communications Source Type: research

Evaluation of cooperative antileukemic effects of nilotinib and vildagliptin in Ph+ chronic myeloid leukemia
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a reciprocal chromosome translocation, t(9;22), which creates the Philadelphia (Ph) chromosome [1 –4]. The resulting BCR/ABL1 fusion gene causes constitutive activation of the BCR/ABL1 kinase and of several downstream signaling pathways [2–6]. As a result, affected cells exhibit enhanced survival and the resulting accumulation of myeloid progenitor cells leads to the clinical picture of CML [2–7]. The development of BCR/ABL1-specific tyrosine kinase inhibitors (TKIs), including imatinib and the second- and third-generation TK...
Source: Experimental Hematology - October 13, 2017 Category: Hematology Authors: Michael Willmann, Irina Sadovnik, Gregor Eisenwort, Martin Entner, Tina Bernthaler, Gabriele Stefanzl, Emir Hadzijusufovic, Daniela Berger, Harald Herrmann, Gregor Hoermann, Peter Valent, Thomas R ülicke Source Type: research

Evaluation of cooperative anti-leukemic effects of nilotinib and vildagliptin in Ph+ chronic myeloid leukemia
• NSG mouse-engrafting CML LSC display CD26 and DPPIV activity• The DPPIV-targeting drug vildagliptin counteracts mobilization of CML LSC• Vildagliptin and sitagliptin did not modulate growth or survival of CML cells• Vildagliptin therapy did not prevent engraftment of CML LSC in NSG mice• Vildagliptin failed to promote TKI effects on CML engraftment in NSG mice (Source: Experimental Hematology)
Source: Experimental Hematology - October 13, 2017 Category: Hematology Authors: Michael Willmann, Irina Sadovnik, Gregor Eisenwort, Martin Entner, Tina Bernthaler, Gabriele Stefanzl, Emir Hadzijusufovic, Daniela Berger, Harald Herrmann, Gregor Hoermann, Peter Valent, Thomas R ülicke Source Type: research

Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate in vitro hematopoietic stem cell migration effectively comparable to beta adrenergic stimulation
• PB and BM microenvironment contain AEA and 2-AG.• BM-MSCs secrete AEA and 2-AG.• BM-MNCs and BM-CD34+HSCs, express CB1, CB2 and β-AR subtypes.• AEA and 2-AG stimulated HSC migration was blocked by CB receptor antagonists.• eCBs might be potential candidates to enhance HSC migration in a clinical setting. (Source: Experimental Hematology)
Source: Experimental Hematology - October 10, 2017 Category: Hematology Authors: Sevil K öse, Fatima Aerts-Kaya, ağla Zübeyde Köprü, Emirhan Nemutlu, Barış Kuşkonmaz, Beren Karaosmanoğlu, Zihni Ekim Taşkıran, Belgin Altun, Duygu Uçkan Çetinkaya, Petek Korkusuz Source Type: research

Characterization and use of the novel human multiple myeloma cell line MC-b11/14 to study biological consequences of CRISPR-mediated loss of immunoglobulin a heavy chain
• A novel human monoclonal IgA kappa myeloma cell line was established.• CRISPR mediated gene editing was used to disrupt IgA heavy chain expression.• Loss of IgA expression, significantly lessened sensitivity to bortezomib. (Source: Experimental Hematology)
Source: Experimental Hematology - October 10, 2017 Category: Hematology Authors: Denise K. Walters, Bonnie K. Arendt, Renee C. Tschumper, Xiaosheng Wu, Diane F. Jelinek Source Type: research

Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies
Next-generation sequencing (NGS) methods have provided unprecedented insights into the somatic mutations associated with hematological malignancies, including myeloproliferative neoplasms (MPNs) [1 –3]. However, although we are now able to acquire detailed lists of mutations present in tumors at a given state of development, we are only beginning to understand how these mutations are associated in tumor subclones and the history of mutation acquisition during tumor development. The relevance of analyzing the makeup of tumors in detail has been demonstrated recently in studies of MPN patients and have shown, for the f...
Source: Experimental Hematology - October 9, 2017 Category: Hematology Authors: Francesca L. Nice, Charlie E. Massie, Thorsten Klampfl, Anthony R. Green Tags: Brief Communications Source Type: research

Determination of complex subclonal structures of haematological malignancies by multiplexed genotyping of blood progenitor colonies
• Complex clonal hierarchies are difficult to predict computationally from next generation sequencing data.• Multiplexed genotyping of burst forming unit-erythroid colonies based on next generation sequencing data allowed for the determination of a complex subclonal composition in a patient with Myeloproliferative neoplasm.• Analysis of subclonal composition allowed for the determination of order of acquisition of mutations. (Source: Experimental Hematology)
Source: Experimental Hematology - October 9, 2017 Category: Hematology Authors: Francesca L. Nice, Charlie E. Massie, Thorsten Klampfl, Anthony R. Green Tags: Brief Communications Source Type: research