Cytogenetic and cytokine profile in elderly patients with cytopenia
The number of elderly populations is on a continuous rise. A significant proportion of elderly patients suffer from anemia. Anemia has been identified as a risk factor for hospitalization and morbidity, especially in the elderly1. The cause of anemia could be multifactorial. Two-third of these patients have nutritional deficiencies and anemia of chronic disease. In one-third of patients, the cause of anemia is unknown. A significant proportion of these patients can represent early or undiagnosed myelodysplastic syndrome (MDS). (Source: Experimental Hematology)
Source: Experimental Hematology - July 30, 2020 Category: Hematology Authors: Dr. Shaila Mathai Kaniyattu, Dr. A Meenakshi, Dr. B Mohana Kumar, Dr. Karuna Ramesh Kumar, Dr. Shama Rao, Dr. D Prashanth Shetty, Dr. Vijith Shetty, Dr. K Jayaprakash Shetty, Dr. Padma K Shetty Source Type: research

Single-cell lineage tracing approaches in hematology research – technical considerations
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the sustained production of mature blood cells during homeostasis and in response to hematopoietic stresses1,2. Aberrant HSPC activity is also linked to a spectrum of hematological diseases, from clonal hematopoiesis to leukemias3-6. The classical models of hematopoiesis predict the existence of a homogeneous pool of multipotent and self-renewing hematopoietic stem cells (HSCs), which are equally contributing to the balanced production of all blood cell lineages through progressive lineage differentiation7,8. (Source: Experimental Hematology)
Source: Experimental Hematology - July 28, 2020 Category: Hematology Authors: Joana Carrelha, Dawn S. Lin, Alejo E. Rodriguez-Fraticelli, Tiago C. Luis, Adam C Wilkinson, Nina Cabezas-Wallscheid, Cedric S. Tremblay, Simon Haas Source Type: research

Is extraembryonic endoderm a source of placental blood cells?
The fertilized egg of placental mammals establishes both the embryo and extraembryonic tissues which support the fetus during gestation. Four extraembryonic tissues, the allantois, chorion, yolk sac, and amnion, create the chorio-allantoic and chorio-vitelline (yolk sac) placentae and are conserved amongst all Placentalia. The allantois matures into the vascularized umbilical cord; the chorion forms the site of exchange between the fetus and its mother; the yolk sac, whose major components are extraembryonic mesoderm and extraembryonic endoderm, called “hypoblast” (humans/non-human primates) or “visceral ...
Source: Experimental Hematology - July 28, 2020 Category: Hematology Authors: Karen M. Downs Source Type: research

Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts
The process of differentiation of hematopoietic stem cells into functional blood cells involves a continuum of organized, stable, and hierarchical intermediate stages ranging from multipotent to unipotent progenitor cells. In the canonical hematopoiesis, megakaryocyte and erythroid lineages are closely related and share a common bipotent megakaryocytic and erythroid progenitor (MEP) [1,2]. Recently, several studies have reported the existence of hematopoietic stem cells (HSCs) with megakaryocyte-biased differentiation potential at the apex of the hematopoietic hierarchy in normal and stress hematopoiesis, suggesting that c...
Source: Experimental Hematology - July 25, 2020 Category: Hematology Authors: Salima Hacein-Bey-Abina, Machadiya Estienne, St éphanie Bessoles, Hamid Echchakir, Magali Pederzoli-Ribeil, Andrada Chiron, Lydia Aldaz-Carroll, Valentin Leducq, Yanyan Zhang, Michèle Souyri, Fawzia Louache, Amine M. Abina Tags: Regular Submission Source Type: research

Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin- dependent and –independent context
The process of differentiation of hematopoietic stem cells into functional blood cells involves a continuum of organized, stable and hierarchical intermediate stages ranging from multipotent to unipotent progenitor cells. In the canonical hematopoiesis, megakaryocyte and erythroid lineages are closely related and share a common bipotent megakaryocytic and erythroid progenitor (MEP) (1, 2). Recently, several studies have demonstrated the existence of hematopoietic stem cells (HSC) with megakaryocyte-biased differentiation potential at the apex of the hematopoietic hierarchy in normal and stress hematopoiesis suggesting that...
Source: Experimental Hematology - July 25, 2020 Category: Hematology Authors: Salima Hacein-Bey-Abina, Machadiya Estienne, St éphanie Bessoles, Hamid Echchakir, Magali Pederzoli-Ribeil, Andrada Chiron, Lydia Aldaz-Carroll, Valentin Leducq, Yanyan Zhang, Michèle Souyri, Fawzia Louache, Amine M. Abina Source Type: research

DEPTOR is a microRNA-155 target regulating migration and cytokine production in diffuse large B-cell lymphoma cells
Diffuse large B-Cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for 30-40% of the newly diagnosed NHLs. DLBCLs are molecularly classified into distinct subtypes that differ concerning the cell of origin, oncogenic mechanisms, and clinical behavior 1-3. In general, DLBCLs can be classified as either activated B-cell (ABC) type, or germinal center B-cell (GCB) type tumors, representing different cell of origin and associated with different prognoses. However, recent studies highlight additional molecular and clinical heterogeneity within each of these subtypes 3,4. (Source: Experimental Hematology)
Source: Experimental Hematology - July 19, 2020 Category: Hematology Authors: Ewa Jab łońska, Emilia Białopiotrowicz, Maciej Szydłowski, Monika Prochorec-Sobieszek, Przemysław Juszczyński, Anna Szumera-Ciećkiewicz Source Type: research

MNDA controls the expression of MCL-1 and BCL-2 in chronic lymphocytic leukemia cells
MNDA (Myeloid Nuclear Differentiation Antigen) is a member of the Hematopoietic Interferon (IFN)-inducible Nuclear proteins with a 200-amino acid repeat (IFI200/HIN-200) family. These factors are also annotated as PYHIN factors due to the presence of an N-terminal pyrin domain (PYD) and C-terminal HIN domain(s) [1-4]. Their expression can be modulated by signalling pathways, including the IFN pathway, and several PYHIN factors relocate to the cytoplasm during the cell cycle or upon induction of stress [5-7]. (Source: Experimental Hematology)
Source: Experimental Hematology - July 15, 2020 Category: Hematology Authors: Stefania Bottardi, Romain Guieze, Vincent Bourgoin, Nasser Fotouhi-Ardakani, Aurore Doug é, Anaïs Darracq, Yahia A. Lakehal, Marc G. Berger, Luigina Mollica, Jacques-Olivier Bay, James G. Omichinski, Eric Milot Source Type: research

Analysis of IL-6 serum levels and CAR T cell-specific digital PCR in the context of cytokine release syndrome
After Swissmedic approval of Kymriah (tisagenlecleucel, Novartis, Basel, Switzerland) in 2018 for chimeric antigen receptor T-cell (CAR-T) therapy for adults with relapsed or refractory (r/r) B-lineage acute lymphoblastoid leukemia (ALL) and high-grade B-cell lymphomas after failure of two or more therapy lines, followed by the approval of Yescarta (axicabtagen ciloleucel, Kite/Gilead, Santa Monica, CA) by Swissmedic in 2019, a growing number of Swiss centers have established CAR-T therapy. In addition, CAR-T therapy is currently being explored for other hematologic malignancies, for example, multiple myeloma [1]. (Source:...
Source: Experimental Hematology - July 13, 2020 Category: Hematology Authors: Thomas Pabst, Raphael Joncourt, Evgenii Shumilov, Alexander Heini, Gertrud Wiedemann, Myriam Legros, Katja Seipel, Christof Schild, Katarzyna Jalowiec, Behrouz Mansouri, Michaela Fux, Urban Novak, Naomi Porret, Sacha Zeerleder, Ulrike Bacher Tags: Brief communication Source Type: research

Analysis of IL-6 serum levels and CAR-T cell specific digital PCR in the context of cytokine release syndrome (CRS)
Following the Swissmedic approval of Kymriah ® (tisagenlecleucel; Novartis) 2018 for chimeric antigen receptor (CAR)-T cell therapy for adults with relapsed or refractory (r/r) B-lineage ALL and high-grade B-cell lymphomas after failure of ≥2 therapy lines, followed by the approval of Yescarta® (axicabtagen ciloleucel, Kite/Gilead) by Swis smedic in 2019, a growing number of Swiss centers have established CAR-T therapy. In addition, CAR-T therapy is currently explored for other hematologic malignancies, e.g. (Source: Experimental Hematology)
Source: Experimental Hematology - July 13, 2020 Category: Hematology Authors: Thomas Pabst, Raphael Joncourt, Evgenii Shumilov, Alexander Heini, Gertrud Wiedemann, Myriam Legros, Katja Seipel, Christof Schild, Katarzyna Jalowiec, Behrouz Mansouri, Michaela Fux, Urban Novak, Naomi Porret, Sacha Zeerleder, Ulrike Bacher Tags: Brief Communication Source Type: research

Lineage commitment of hematopoietic stem cells and progenitors: insights from recent single cell and lineage tracing technologies
The hematopoietic system plays a major role in human health and disease, supplying oxygen and nutrients to tissues, supporting healing, and fighting infections. These essential functions are carried out by the various types of mature hematopoietic cells, including red blood cells, platelets, myeloid immune cells (macrophages, neutrophils), and lymphocytes (T cells, B cells, natural killer [NK] cells). Most of the mature cells lack the ability to proliferate and have limited lifespans, so they must be constantly replenished by a process called hematopoiesis (Eaves, 2015; Orkin and Zon, 2008). (Source: Experimental Hematology)
Source: Experimental Hematology - July 8, 2020 Category: Hematology Authors: Stephen Loughran, Simon Haas, Adam C. Wilkinson, Allon Klein, Marjorie Brand Tags: Perspective Source Type: research

TLR2/6 signaling promotes the expansion of premalignant hematopoietic stem and progenitor cells in the NUP98-HOXD13 mouse model of MDS
The myelodysplastic syndromes are a group of hematopoietic stem and progenitor cell (HSPC) disorders characterized by abnormal hematopoiesis and a high risk of transformation to acute leukemia.1,2 Numerous prior studies have described enhanced innate immune signaling, and in particular, increased toll like receptor (TLR) signaling, in the CD34+ stem and progenitor cells of patients with MDS.3-11 This enhanced TLR signaling is thought to contribute to the ineffective hematopoiesis and cell death that is a prominent feature of lower-risk disease. (Source: Experimental Hematology)
Source: Experimental Hematology - July 8, 2020 Category: Hematology Authors: Darlene A. Monlish, Zev J. Greenberg, Sima T. Bhatt, Kathryn M. Leonard, Molly P. Romine, Qian Dong, Lauren Bendesky, Eric J. Duncavage, Jeffrey A. Magee, Laura G. Schuettpelz Source Type: research

Enhancing mitochondrial function in vivo rescues MDS-like anemia induced by pRb deficiency
Erythropoiesis, the formation of red blood cells (RBCs), is a tightly regulated multi-step process fundamental to life by transporting oxygen to all cells and tissues. RBCs are continuously replenished from the bone marrow (BM) where multi-potent hematopoietic stem cells (HSCs) differentiate through intermediates including megakaryocytic-erythroid progenitors (MegE), erythroid burst-forming-units (BFU-Es) and erythroid colony-forming-units (CFU-Es)1. This expansion phase of erythroid commitment is followed by terminal differentiation in which CFU-Es generate erythroblasts that undergo stepwise morphological changes, includ...
Source: Experimental Hematology - July 3, 2020 Category: Hematology Authors: Taha Sen, Mayur Jain, Magnus Gram, Alexander Mattebo, Shamit Soneji, Carl R Walkley, Sofie Singbrant Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - July 1, 2020 Category: Hematology Source Type: research

Characterization of resistance to a recombinant hexameric Fas-ligand (APO010) in human cancer cell lines
Multiple myeloma (MM) is a synonym for malignant neoplasm of plasma cells in the bone marrow and is the second most common hematological malignancy. The incidence of MM is about 6 to 8 out of 100.000 in Western Countries and in Denmark approximately 300 new patient cases are diagnosed annually. The MM patients are typically aged above 65-70 years. (Source: Experimental Hematology)
Source: Experimental Hematology - June 30, 2020 Category: Hematology Authors: Haatisha Jandu, Annette Nielsen, Nils Brunner, Anker Hansen, Steen Knudsen, Jan Stenvang, Peter B. Jensen Source Type: research

The transcription factor NFE2 enhances expression of the hematopoietic master regulators SCL/TAL1 and GATA2
The hematopoietic transcription factor Nuclear Factor Erythroid-2 (NFE2) plays a role in the pathophysiology of myeloproliferative neoplasms (MPN) as the majority of MPN patients show increased NFE2 levels and elevated NFE2 expression recapitulates MPN hallmarks in vitro and in vivo.1-4 In transgenic mice, NFE2 overexpression effects an MPN phenotype with thrombocytosis, leukocytosis, Epo-independent colony formation, expansion of the stem- and progenitor cell compartment and spontaneous transformation to acute myeloid leukemia. (Source: Experimental Hematology)
Source: Experimental Hematology - June 24, 2020 Category: Hematology Authors: Laura C. Siegwart, Sven Schwemmers, Julius Wehrle, Christoph Koellerer, Thalia Seeger, Albert Gr ünder, Heike L. Pahl Source Type: research

MLLT10 in benign and malignant hematopoiesis
Each highly specified, functional member of the hematopoietic system is derived from a common progenitor: the hematopoietic stem cell (HSC) (reviewed in [1, 2]). HSCs have an indeterminate self-renewal capacity and give rise to progeny which become committed to the lymphoid or myeloid pathways, before terminally differentiating into functional members of the circulatory system [3-5]. This process is highly dependent on growth factors and transcription factors (TFs) which regulate gene expression patterns and facilitate these steps of commitment and differentiation [6-8]. (Source: Experimental Hematology)
Source: Experimental Hematology - June 19, 2020 Category: Hematology Authors: Jamie L. Deutsch, Jessica L. Heath Tags: Review Source Type: research

AML chemoresistance: The role of mutant TP53 subclonal expansion and therapy strategy
Acute myeloid leukemia (AML) is an aggressive maliganancy characterized by uncontrolled proliferation and accumulation of immature myeloid precursor cells in the bone marrow leading to hematopoietic failure. Cytarabine (Ara-C) has been the backbone of the standard chemotherapy agent of induction therapy and consolidation therapy for AML since the 1960s. Despite the high initial remission rated with newly diagnosed AML patients, over 50% of first complete remission patients are expected to relapse within 3 years [1]. (Source: Experimental Hematology)
Source: Experimental Hematology - June 19, 2020 Category: Hematology Authors: Bowen Yan, David Claxton, Suming Huang, Yi Qiu Tags: Perspective Source Type: research

Engineering of targeted megabase-scale deletions in human induced pluripotent stem cells
Recurrent chromosomal deletions are frequently associated with human diseases. Hematologic malignancies, in particular, often harbor focal deletions, most commonly in the hemizygous state. These may drive disease by providing one of two hits toward complete gene inactivation or through haplo-insufficiency of one or more genes. Deletion of the long arm of chromosome 7q (del7q) is a common cytogenetic abnormality in patients with hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). (Source: Experimental Hematology)
Source: Experimental Hematology - June 12, 2020 Category: Hematology Authors: Andriana G. Kotini, Eirini P. Papapetrou Tags: Original Research Source Type: research

Engineering of targeted megabase-scale deletions in human iPSCs
Recurrent chromosomal deletions are frequently associated with human diseases. Hematologic malignancies, in particular, often harbor focal deletions, most commonly at hemizygous state. These may drive disease by providing one of two hits towards complete gene inactivation or through haploinsufficiency of one or more genes. Deletion of the long arm of chromosome 7q (del7q) is a common cytogenetic abnormality in patients with hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). (Source: Experimental Hematology)
Source: Experimental Hematology - June 12, 2020 Category: Hematology Authors: Andriana G Kotini, Eirini P Papapetrou Source Type: research

ZBTB7A links tumor metabolism to myeloid differentiation
ZBTB7A is a transcription factor with an important role in the regulation of linage fate decisions (1) and glycolysis (2). Pandolfi and colleagues performed most of the early research on Zbtb7a, also known as leukemia-related factor (Lrf). Using both Zbtb7a complete knockout (KO) and conditional hematopoietic KO mice, they could show that Zbtb7a influences all three branches of hematopoietic differentiation. First, Zbtb7a expression is indispensable for erythroid development, where it represses Bim-mediated apoptosis (3) and binds gene targets of the key erythroid transcription factor Gata1 (4). (Source: Experimental Hematology)
Source: Experimental Hematology - June 7, 2020 Category: Hematology Authors: Enric Redondo Monte, Paul Kerbs, Philipp A. Greif Tags: Perspective Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - June 1, 2020 Category: Hematology Source Type: research

Assessment and streamlined preparation of low-cytotoxicity lentiviral vectors for mobilized human hematopoietic stem cell transduction
Recombinant lentiviruses serve as important tools for diverse applications in vitro and in vivo. In research contexts, examples include ectopic protein expression [1], shRNA inhibition of targeted transcripts [2], gRNA/Cas9 CRISPR lentivirus libraries [3], and progenitor cell barcoding for lineage and tumor cell tracking studies [4,5]. In clinical trials, significant progress is being made with lentiviruses as gene therapy vectors for select inherited diseases (e.g., thalassemia, X-linked severe combined immunodeficiency [SCIDX-1]) [6,7] and for chimeric antigen receptor (CAR) T-cell engineering [8]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 26, 2020 Category: Hematology Authors: Paul T. Toran, Martin Wohlfahrt, Julia Foye, Hans-Peter Kiem, Don M. Wojchowski Tags: Methods/techniques Source Type: research

Assessment, and streamlined preparation of low cytotoxicity lentiviral vectors for mobilized human hematopoietic stem cell transduction
Recombinant lentiviruses serve as important tools for diverse applications in vitro and in vivo. In research contexts, examples include ectopic protein expression [1], shRNA inhibition of targeted transcripts [2], gRNA / Cas9 CRISPR lentivirus libraries [3], and progenitor cell barcoding for lineage and tumor cell tracking studies [4, 5]. In clinical trials, significant progress is being made with lentiviruses as gene therapy vectors for select inherited diseases (e.g., thalassemia, SCIDX-1) [6, 7] and for CAR-T cell engineering [8]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 26, 2020 Category: Hematology Authors: Paul T. Toran, Martin Wohlfahrt, Julia Foye, Hans-Peter Kiem, Don M. Wojchowski Source Type: research

Erratum to “Molecular characterization of sorted malignant B cells from patients clinically identified with mantle cell lymphoma” [Experimental Hematology 84 (2020) 7–18]
The publisher regrets that during production, Figures 3 and 5, Supplementary Figures, and the Graphical Abstract were changed during the typesetting process and published incorrectly. (Source: Experimental Hematology)
Source: Experimental Hematology - May 23, 2020 Category: Hematology Authors: Marcus H øy Hansen, Oriane Cédile, Mia Koldby Blum, Simone Valentin Hansen, Lene Hyldahl Ebbesen, Hans Herluf Nørgaard Bentzen, Mads Thomassen, Torben A. Kruse, Stephanie Kavan, Eigil Kjeldsen, Thomas Kielsgaard Kristensen, Jacob Haaber, Niels Abildgaa Tags: Erratum Source Type: research

Combined G-CSF and Plerixafor enhance hematopoietic recovery of CD34+ cells from poor mobilizer patients in NSG mice
Hematopoietic stem/progenitor cells (HSPC) contained in the CD34+ cell compartment give rise to all blood cell types and have been used for decades in transplantation [1, 2]. Nowadays, the main source of transplantable HSC comes from G-CSF-mobilized peripheral blood and the minimal number of mobilized CD34+ cells (mCD34+) for autologous transplantation is 2.106 CD34+ cells/kg body weight [3]. Moreover, up to 30% patients fail to mobilize enough CD34+ cells after G-CSF treatment [4-6]. The combination of G-CSF plus Plerixafor, a CXCR4 chemokine receptor inhibitor, was shown to improve and increase the number of mCD34+ [7], ...
Source: Experimental Hematology - May 22, 2020 Category: Hematology Authors: M.L. Arcangeli, P. Brault, J.H. Bourhis, F. Kuhnowski, E. Henry, V. Barroca, S. Koscielny, F. Pflumio, S. Amsellem Source Type: research

Regulation of CD71+TER119+ erythroid progenitor cells by CD45
Erythrocytes are one of the most abundant cells in the body that play a vital role in the transportation of oxygen in the circulatory system. Due to their limited life span of approximately 120 days in humans and 40 days in mice, erythrocytes need to be replenished daily 1. Healthy adults have been reported to produce over 2 million erythrocytes each second 1. (Source: Experimental Hematology)
Source: Experimental Hematology - May 21, 2020 Category: Hematology Authors: Yaein A. Shim, Teresa Campbell, Asanga Weliwitigoda, Manisha Dosanjh, Pauline Johnson Source Type: research

Apoptotic events induced by a natural plastoquinone from the marine alga Desmarestia menziesii in lymphoid neoplasms
Lymphoid neoplasms are clonal expansions of lymphoid cells at various stages of differentiation. T-Cell acute lymphoblastic leukemia (T-ALL) and Burkitt's lymphoma (BL) are aggressive forms of immature and mature lymphoid neoplasms. The chemotherapy protocols available for these diseases are associated with frequent relapses and high morbidity and mortality rates [1 –4]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 15, 2020 Category: Hematology Authors: Iris Mattos Santos-Pirath, Laura Otto Walter, Mariana Franzoni Maioral, Ana Cl áudia Philippus, Gabriele Andressa Zatelli, Paulo Antunes Horta, Pio Colepicolo, Miriam De Barcellos Falkenberg, Maria Cláudia Santos-Silva Tags: Regular submission Source Type: research

A Sticky Wicket: Defining Molecular Functions for CD34 in Hematopoietic Cells
CD34, one of the best known and clinically important markers of hematopoietic progenitor cells, was first identified as a surface antigen expressed on the myeloblastic cell line KG-1a and a subpopulation (1-2%) of ‘normal’ human bone marrow (BM) containing most (∼95%) of the myeloid and erythroid lineage-committed progenitors [1]. We now know that CD34 marks resident progenitor cells for a diverse array of tissues including blood, stroma/fibro/adipocyte progenitors (FAPs), skeletal muscle, skin (keratoc ytes), endothelia and dermal epithelia (reviewed in ref [2]). (Source: Experimental Hematology)
Source: Experimental Hematology - May 15, 2020 Category: Hematology Authors: Michael R. Hughes, Diana Canals Hernaez, Jessica Cait, Ido Refaeli, Bernard Lo, Calvin Roskelley, Kelly M. McNagny Tags: Review Source Type: research

Apoptotic events induced by a natural plastoquinone from marine algae Desmarestia menziesii on lymphoid neoplasms
Lymphoid neoplasms are clonal expansions of lymphoid cells at various stages of differentiation. T-cell acute lymphoblastic leukemia (T-ALL) and burkitt lymphoma (BL) are aggressive forms of immature and mature lymphoid neoplasm. The chemotherapy protocols available for these diseases are associated with frequent relapses and high morbidity and mortality rates [1-4]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 15, 2020 Category: Hematology Authors: Iris Mattos Santos-Pirath, Laura Otto Walter, Mariana Franzoni Maioral, Ana Cl áudia Philippus, Gabriele Andressa Zatelli, Paulo Antunes Horta, Pio Colepicolo, Miriam De Barcellos Falkenberg, Maria Cláudia Santos-Silva Source Type: research

Variability in the cleavage of exosome-associated transferrin receptor questions the utility of clinically useful soluble transferrin assays for dogs, cats, and horses
Transferrin receptor 1 (TfR) is a transmembrane glycoprotein that functions in the cellular procurement of iron through endocytosis of the iron –transferrin–TfR complex [1–4]. TfR is found in high numbers on erythrocyte precursors because of their high demand for iron to support hemoglobin production [2–5]. As erythrocyte precursors mature from reticulocytes to mature erythrocytes, their iron demand, and thus TfR requirement, ceases and TfR is sorted into exosomes and released along with other obsolete membrane proteins [2,5–12]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 14, 2020 Category: Hematology Authors: Caitlyn R. Martinez, Kelly S. Santangelo, Christine S. Olver Tags: Regular submission Source Type: research

Variability in the cleavage of exosomal-associated transferrin receptor questions the utility of clinically useful soluble transferrin assays for dogs, cats and horses
Transferrin receptor 1 (TfR) is a transmembrane glycoprotein that functions in the cellular procurement of iron through the endocytosis of the iron-transferrin-TfR complex.1 –4 TfR is found in high numbers on erythrocyte precursors due to their high demand for iron to support hemoglobin production.2–5 As erythrocyte precursors mature from reticulocytes to mature erythrocytes, their iron demand, and thus TfR requirement, ceases and TfR is sorted into exosomes and rel eased along with other obsolete membrane proteins. (Source: Experimental Hematology)
Source: Experimental Hematology - May 14, 2020 Category: Hematology Authors: Caitlyn R. Martinez, Kelly S. Santangelo, Christine S. Olver Source Type: research

Epigenetic regulation of protein translation in KMT2A-rearranged AML
Rearrangements of KMT2A (MLL1) occur in 10% of persons with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and in 70% of cases of infant ALL. With few exceptions, KMT2A rearrangements are associated with a poor prognosis, and KMT2A-rearranged (KMT2A-r) leukemias have been the target of substantial drug development efforts and clinical research without much impact yet on survival [1]. KMT2A fusions are strongly transforming [2], likely because of the profound epigenetic changes they induce. (Source: Experimental Hematology)
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Alexandra Lenard, Hongbo Michael Xie, Taylor Pastuer, Tyler Shank, Clara Libbrecht, Molly Kingsley, Simone S. Riedel, Zuo-Fei Yuan, Nan Zhu, Tobias Neff, Kathrin M. Bernt Tags: Regular Submission Source Type: research

Prdm3 and Prdm16  cooperatively maintain hematopoiesis and clonogenic potential
The genesis of mature blood cells in the adult bone marrow originates with multipotent self-renewing hematopoietic stem cells (HSCs), which reside at the top of an orchestrated but heterogeneous hierarchy of successive lineage commitment steps leading to oligolineage progenitors [1]; this process results in the production of mature circulating erythrocytes, platelets, and immune defense cells that populate the peripheral blood and immune organs. The regulation of this process is under the control of both intrinsic and extrinsic factors that drive, direct, and fine-tune this process in response to the needs of the organism....
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Kelly A. McGlynn, Rongli Sun, Alin Vonica, Sarah Rudzinskas, Yi Zhang, Archibald S. Perkins Tags: Regular Submission Source Type: research

Cyclosporine enhances the sensitivity to lenalidomide in MDS/AML in vitro
Lenalidomide (LEN) is used for the treatment of multiple myeloma (MM) and lower-risk myelodysplastic syndromes (MDS) that harbor deletion of chromosome 5q (del(5q))[1]. Clinical trials reveal poor response to LEN in patients with higher-risk MDS or acute myeloid leukemia (AML) with or without del(5q)[2, 3]. Understanding the molecular mechanism of the action of LEN will provide novel insights into its therapeutic implications in hematologic malignancies. Recent studies demonstrated that LEN directly binds cereblon (CRBN), a component of the CRL4 E3 ubiquitin ligase complex, resulting in ubiquitination and subsequent degrad...
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Xiaofei He, Aixia Dou, Saran Feng, Ashley Roman-Rivera, Caleb Hawkins, Lauren Lawley, Jiajia Zhang, Mark Wunderlich, Benjamin Mizukawa, Stephanie Halene, Amisha Patel, Jing Fang Tags: Brief Communication Source Type: research

Signaling properties of murine MPL and MPL mutants after stimulation with thrombopoietin and romiplostim
All our blood cells are produced from HSC in the bone marrow (BM). HSC have the potential to self-renew but also to differentiate into all mature blood cell lineages. These processes are guided by extracellular cues, including cytokines and their receptors. Among them, THPO and its receptor MPL control megakaryopoiesis, but also HSC maintenance, quiescence and post-transplant expansion [1 –3]. MPL was identified as the cellular homologue of the myeloproliferative leukemia virus oncogene v-Mpl [4, 5] and is a type one cytokine receptor similar to the erythropoietin (EPO) receptor. (Source: Experimental Hematology)
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Marcel G E Rommel, Keven Hoerster, Christian Milde, Franziska Schenk, Luise Roser, Saskia Kohlscheen, Niels Heinz, Ute Modlich Source Type: research

Epigenetic regulation of protein translation in KMT2A- rearranged AML
Rearrangements of KMT2A (MLL1) occur in 10% of AML and ALL, and 70% of infant ALL. With few exceptions, KMT2A rearrangements are associated with a poor prognosis, and KMT2A-rearranged (KMT2A-r) leukemias have been the target of substantial drug development efforts and clinical research without much impact yet on survival 1. KMT2A fusions are strongly transforming 2, likely due to the profound epigenetic changes they induce. Key histone lysine methyltransferases (KMTs) involved in KMT2A-fusion mediated leukemogenesis are the H3K79 KMT4 (hereafter referred to as DOT1L) 3-6 and the H3K27 KMT6 (hereafter referred to as EZH2) 7...
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Alexandra Lenard, Hongbo Michael Xie, Taylor Pastuer, Tyler Shank, Clara Libbrecht, Molly Kingsley, Simone S. Riedel, Zuo-Fei Yuan, Nan Zhu, Tobias Neff, Kathrin M. Bernt Source Type: research

Development of embryonic and adult leukemia mouse models driven by MLL-ENL translocation
The myeloid-lymphoid or mixed lineage leukemia gene (MLL/kmt2a) has a major contribution to aggressive acute leukemias in the 85% of infant (18 yrs old) (Sam et al., 2012; Winters and Bernt, 2017). (Source: Experimental Hematology)
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Roshani Sinha, Cristina Porcheri, Teresa d'Altri, Jessica Gonz ález, Cristina Ruiz Herguido, Terry Rabbits, Lluis Espinosa, Anna Bigas Salvans Tags: Brief Communication Source Type: research

Lightening the way of hematopoiesis: infrared laser-mediated lineage tracing with high spatial-temporal resolution
Hematopoiesis is a vital developmental process, in which all blood cells including erythrocytes and leukocytes are generated. It has long been recognized that vertebrate hematopoiesis occurs in multiple waves in various anatomic sites. In mammals, the first or primitive wave of hematopoiesis initiates in the yolk sac (YS) and generates predominantly erythrocytes and macrophages [1]. Shortly after the primitive hematopoiesis, a transient erythroid/myeloid progenitor (EMP) population was observed in the YS [2,3]. (Source: Experimental Hematology)
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Sicong He, Jin Xu, Jianan Y. Qu, Zilong Wen Tags: Perspective Source Type: research

Prdm3 and Prdm16 cooperatively maintain hematopoiesis and clonogenic potential
The genesis of mature blood cells in the adult bone marrow originates with multipotent self-renewing hematopoietic stem cells (HSCs), which reside at the top of an orchestrated but heterogeneous hierarchy of successive lineage commitment steps into oligolineage progenitors [1]; this process results in the production of mature circulating erythrocytes, platelets, and immune defense cells that populate the peripheral blood and immune organs. The regulation of this process is under the control of both intrinsic and extrinsic factors that drive, direct, and fine-tune this process in response to the needs of the organism. (Sour...
Source: Experimental Hematology - May 10, 2020 Category: Hematology Authors: Kelly A. McGlynn, Rongli Sun, Alin Vonica, Sarah Rudzinskas, Yi Zhang, Archibald S. Perkins Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - May 1, 2020 Category: Hematology Source Type: research

Single-Cell Transcriptome in Chronic Myeloid Leukemia: Pseudotime Analysis Reveals Evidence of Embryonic and Transitional Stem Cell States
Chronic myeloid leukemia (CML) is a clonal hematopoietic malignancy, characterized by acquisition of the t(9;22) translocation leading to Ph1 chromosome and its counterpart BCR-ABL oncogene, in a very primitive hematopoietic stem cell [1]. CML is a model of targeted therapies as the proof of concept of the feasibility of targeting the tyrosine kinase (TK) activity BCR-ABL using TK inhibitors (TKIs) has been found to lead to major responses and remissions [2]. The use of imatinib and, later, second-generation [3,4] and third-generation [5] TKI therapies has changed the natural history of the disease and prolonged overall su...
Source: Experimental Hematology - April 28, 2020 Category: Hematology Authors: Sarah Pagliaro, Christoph Desterke, Herve Acloque, Jean Claude Chomel, Lucas de Souza, Patricia Hugues, Frank Griscelli, Adlen Foudi, Annelise Bennaceur-Griscelli, Ali G. Turhan Tags: Regular submission Source Type: research

Single cell transcriptome in chronic myeloid leukemia (cml): pseudotime analysis reveals evidence of embryonic and transitional stem cell states
Chronic myeloid leukemia is a clonal hematopoietic malignancy, characterized by the acquisition of the t (9;22) translocation leading to Ph1 chromosome and its counterpart BCR-ABL oncogene, in a very primitive hematopoietic stem cell (Houshmand M et al, 2019). CML is a model of targeted therapies as the proof of concept of the feasibility of targeting the tyrosine kinase (TK) activity BCR-ABL using TK inhibitors (TKI) has been shown to lead to major responses and remissions(Deininger et al., 2009) . (Source: Experimental Hematology)
Source: Experimental Hematology - April 28, 2020 Category: Hematology Authors: S. Pagliaro, C. Desterke, H. Acloque, J.C. Chomel, L de Souza, P. Hugues, F. Griscelli, A. Foudi, A. Bennaceur-Griscelli, A.G. Turhan Source Type: research

Erratum to “Lipocalin-2 levels in acute and chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation”[Experimental Hematology 74 (2019) 25–32]
The publisher regrets that Andreas Winkler's affiliation was incorrect. The correct affiliation for Andreas Winkler is: (Source: Experimental Hematology)
Source: Experimental Hematology - April 20, 2020 Category: Hematology Authors: Alexander Hermann, Andreas Winkler, Christopher Paschen, Zoya Kuzmina, Anastasiya Hladik, Suphan Icme, Oliver Robak Tags: Erratum Source Type: research

Erratum to “Detection of T315I using digital PCR in allogeneic transplant recipients with Ph-positive ALL in the dasatinib era”
The publisher regrets that the title was incorrect. (Source: Experimental Hematology)
Source: Experimental Hematology - April 20, 2020 Category: Hematology Authors: Yu Akahoshi, Hideki Nakasone, Koji Kawamura, Machiko Kusuda, Shunto Kawamura, Junko Takeshita, Nozomu Yoshino, Yukiko Misaki, Kazuki Yoshimura, Ayumi Gomyo, Aki Tanihara, Masaharu Tamaki, Shun-ichi Kimura, Shinichi Kako, Yoshinobu Kanda Tags: Erratum Source Type: research

Obituary Rolf Neth 1926 –2020
With great sadness, we learned of the passing of Professor Dr. Med. Rolf-Dietmar Neth, the founder of the Wilsede Meeting, on March 17, 2020, at the age of 93. He is survived by his wife of 62 years, Hanne-Lore, four sons, and several grandchildren. (Source: Experimental Hematology)
Source: Experimental Hematology - April 10, 2020 Category: Hematology Authors: Boris Fehse, Nicolaus Kr öger, Carol Stocking, Axel Zander Tags: Obituary Source Type: research

Profiling and Bioinformatics Analyses Reveal Chronic Lymphocytic Leukemia Cells Share a Unique Circular RNA Expression Pattern
The role of non-coding RNA (ncRNAs) in the pathogenesis of human diseases was first discovered in chronic lymphocytic leukemia (CLL) [1]. While trying to identify tumor suppressor genes located on chromosome 13q14, which is deleted in approximately 50% of patients, Callin et al. found that the minimal deleted region in patients with CLL and 13q14 deletion includes the coding sequence for microRNAs (miRs) miR-15a and miR-16-1 [1]. Since then, other studies have shown that dysregulation of the miR transcriptome is a hallmark of CLL cells [2]. (Source: Experimental Hematology)
Source: Experimental Hematology - April 10, 2020 Category: Hematology Authors: Oshrat Raz, Galit Granot, Metsada Pasmanik-Chor, Pia Raanani, Uri Rozovski Tags: Brief Communication Source Type: research

Obituary Rolf Neth 1926-2020
Dear Wilsede Community, (Source: Experimental Hematology)
Source: Experimental Hematology - April 10, 2020 Category: Hematology Authors: Boris Fehse, Nicolaus Kr öger, Carol Stocking, Axel Zander Source Type: research

Phospho-proteomic discovery of novel signal transducers including thioredoxin-interacting protein as mediators of erythropoietin-dependent human erythropoiesis
The production of erythroid progenitors requires signals provided by erythropoietin (EPO) and its JAK2-coupled receptor, EPOR [1]. Recombinant human (rh)EPO and related EPOR agonists are also important therapeutics for the anemia of chronic kidney disease [2], myelodysplastic syndrome [3], and chemotherapy [4]. While EPO actions have accordingly been intensely studied [5,6], an advanced understanding of EPO/EPOR/JAK2 effects is important for several reasons. Clinically, and via poorly understood mechanisms, EPO also elicits hypertensive and thrombolytic side effects [7]. (Source: Experimental Hematology)
Source: Experimental Hematology - April 4, 2020 Category: Hematology Authors: Matthew A. Held, Emily Greenfest-Allen, Edward Jachimowicz, Christian J. Stoeckert, Matthew P. Stokes, Antony W. Wood, Don M. Wojchowski Tags: Regular submission Source Type: research

Phospho-Proteomic Discovery of Novel EPO Signal Transducers Including TXNIP as a Mediator of EPO- Dependent Human Erythropoiesis
The production of erythroid progenitors requires signals provided by EPO and its JAK2- coupled receptor, EPOR3. rh-EPO and related EPOR agonists are also important therapeutics for the anemia of chronic kidney disease4, myelodysplastic syndrome5 and chemotherapy6. While EPO's actions have accordingly been intensely studied7,8, an advanced understanding of EPO/EPOR/JAK2 effects is important for several reasons. Clinically, and via poorly understood mechanisms, EPO also elicits hypertensive and thrombolytic side effects9. (Source: Experimental Hematology)
Source: Experimental Hematology - April 4, 2020 Category: Hematology Authors: Matthew A. Held, Emily Greenfest-Allen, Edward Jachimowicz, Christian J. Stoeckert, Matthew P. Stokes, Antony W. Wood, Don M. Wojchowski Tags: Normal Hematopoiesis Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - April 1, 2020 Category: Hematology Source Type: research