Single-cell analysis of erythropoiesis in Rpl11 haploinsufficient mice reveals insight into the pathogenesis of Diamond Blackfan anemia
Diamond-Blackfan anemia (DBA) is a congenital macrocytic anemia. Since mutations resulting in the haploinsufficiency of one of 19 ribosomal proteins cause the same clinical phenotype – marrow erythroid hypoplasia, low reticulocyte count, low red cell numbers, low hemoglobin, low hematocrit, high mean cell volume (MCV), and normal or near normal white blood cell and platelet counts [1, 2] – shared pathways that are uniquely important for red cell differentiation must be impac ted. As an example, ribosomal protein imbalance can increase p53 activity, which preferentially impairs red cell differentiation [3-6]. (S...
Source: Experimental Hematology - February 21, 2021 Category: Hematology Authors: Raymond T. Doty, Xiaowei Yan, Changting Meng, Christopher Lausted, Qiang Tian, Janis L. Abkowitz Source Type: research

The delta isoform of PI3K predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) characterized by monocytic proliferation in the presence of other cytopenias, splenomegaly and propensity for transformation to AML. Prognosis is generally poor, with a mean overall survival between 2-5 years.1 Response to conventional treatment is variable, and the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT). Preclinical observations of hypersensitivity to janus kinase/signal transducer and activator of transcription (JAK/STAT)-dependent GM-CSF signaling in CM...
Source: Experimental Hematology - February 19, 2021 Category: Hematology Authors: Matthew T. Villaume, M. Pia Arrate, Haley E. Ramsey, Kathryn I. Sunthankar, Matthew T. Jenkins, Tamara K. Moyo, Brianna N. Smith, Melissa A. Fischer, Merrida A. Childress, Agnieszka E. Gorska, P. Brent Ferrell, Michael R. Savona Tags: Malignant Hematopoiesis Source Type: research

Bortezomib enhances G-CSF-induced hematopoietic stem cell mobilization by decreasing CXCL12 levels and increasing vascular permeability
Autologous hematopoietic stem cell transplantation (ASCT) with high-dose chemotherapy is a standard therapy for multiple myeloma [1-3] and relapsed non-Hodgkin's lymphoma [4-6]. For rapid hematopoietic recovery after ASCT, it is essential to collect and infuse a sufficient number of hematopoietic stem and progenitor cells (HSPCs). Administration of granulocyte colony-stimulating factor (G-CSF) induces HSPC mobilization from bone marrow (BM) to peripheral blood (PB). However, there are 5 –30% of patients, referred to as poor mobilizers, who are unable to collect adequate numbers of HSPCs by G-CSF [7, 8]. (Source: Experimental Hematology)
Source: Experimental Hematology - February 19, 2021 Category: Hematology Authors: Taichi Matsumoto, Yasushi Takamatsu, Hanae Moriyama, Kazuki Terada, Masayoshi Mori, Kazuhiko Ono, Keisuke Migita, Shuuji Hara Source Type: research

Human CD34-negative Hematopoietic Stem Cells: The Current Understanding of Their Biological Nature
Fluorescence-activated cell sorting (FACS) technology has markedly progressed over the past three decades. Consequently, it is now possible to prospectively purify murine and human hematopoietic stem cells (HSCs) using a combination of suitable cell surface markers. The surface immuno-phenotype of murine HSCs has been thoroughly characterized, resulting in successful single-cell transplantation analyses. (Source: Experimental Hematology)
Source: Experimental Hematology - February 18, 2021 Category: Hematology Authors: Yoshiaki Sonoda Source Type: research

Serum Metabolomic Profiling Correlated with ISS and Clinical Outcome for Multiple Myeloma Patients Treated with High-dose Melphalan and Autologous Stem Cell Transplantation
Multiple myeloma (MM) is the second most common hematologic malignancy, with a yearly incidence of approximately 700 cases in Sweden (1). Even with commonly occurring disease manifestations, there is a large variance in the combination of symptoms, signs, and clinical outcomes. Over the last 20 years, there has been a radical improvement in the treatment results, which is partially due to the development of several new effective drugs (2). Similar to other malignant diseases, genetic aberrations that are potential high-risk markers for more aggressive MM have been identified (3). (Source: Experimental Hematology)
Source: Experimental Hematology - February 17, 2021 Category: Hematology Authors: Ljupco Veskovski, Per-Ola Andersson, Ingemar Turesson, Daniel Malmodin, Anders Pedersen, Ulf-Henrik Mellqvist Source Type: research

Two faces of RUNX3 in myeloid transformation
RUNX transcription factors are critical for development and normal tissue homeostasis and have been characterized as oncogenes or tumor suppressors in the pathogenesis of various tumors 1,2. RUNX family members, including RUNX1, RUNX2, and RUNX3, are highly conserved in the runt domain, which binds to the consensus DNA sequence and is involved in dimerization with the common co-factor CBF β. Loss-of-function mutations in and the deletion of RUNX1 are frequently observed in myeloid malignancies, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) 3,4. (Source: Experimental Hematology)
Source: Experimental Hematology - February 15, 2021 Category: Hematology Authors: Takako Yokomizo-Nakano, Goro Sashida Tags: Review Source Type: research

To Bi or not to Bi: Acute Erythroid Leukemias and hematopoietic lineage choice
Acute erythroid leukemia (AEL) is a subtype of acute myeloid leukemia (AML), representing (Source: Experimental Hematology)
Source: Experimental Hematology - February 15, 2021 Category: Hematology Authors: Cristina di Genua, Claus Nerlov Tags: Review Source Type: research

Distinct effects of chondroitin sulfate on hematopoietic cells and the stromal microenvironment in bone marrow hematopoiesis
In bone marrow (BM) hematopoiesis, it is well known that self-renewal, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPCs) are regulated by the microenvironment called the BM niche, which is affected by the interactions between hematopoietic cells and stromal cells. The BM niche mainly consists of two anatomically distinct cellular entities, the “endosteal niche” and the “vascular niche”. HSPCs can move through these two regions and interact with the extracellular matrix (ECM) components. (Source: Experimental Hematology)
Source: Experimental Hematology - February 11, 2021 Category: Hematology Authors: Takayuki Katagiri, Shun Uemura, Takashi Ushiki, Yaeko Nakajima-Takagi, Motohiko Oshima, Tadahisa Mikami, Asami Kawasaki, Hajime Ishiguro, Tomoyuki Tanaka, Hirohito Sone, Hiroshi Kitagawa, Michihiro Igarashi, Atsushi Iwama, Masayoshi Masuko Source Type: research

Yin and Yang: The dual effects of interferons on hematopoiesis
Interferons (IFNs) are a group of signaling proteins primarily made and released by immune cells upon interaction with pathogens or cancer cells, but can be produced by most other cell types [1, 2]. Interferon production can also be induced endogenously by sensing self-ligands (i.e. dsDNA and dsRNA) or through TLR agonists [3]. These cellularly intrinsic stimuli induce the cGAS/STING (DNA) or RIG-I and MDA5 (RNA) pathways to maintain steady-state interferon production during homeostasis [3]. While IFNs are expressed at low levels in the body at baseline, members of the IFN family are induced to differing degrees depending ...
Source: Experimental Hematology - February 7, 2021 Category: Hematology Authors: Yasmin Demerdash, Bailee Kain, Marieke A.G. Essers, Katherine Y. King Tags: Review Source Type: research

TLR7/8 Agonist Treatment Induces an Increase in Bone Marrow Resident Dendritic Cells and Hematopoietic Progenitor Expansion and Mobilization
Zbtb46gfp (129S-Zbtb46tm1Kmm/J) and B6.Cg-Zbtb46tm3.1(cre)Mnz/J mice were obtained from The Jackson Laboratory. B6.Cg-Zbtb46tm3.1(cre)Mnz/J mice were bred with B6.129P2(SJL)-Myd88tm1Defr/J mice to generate Zbtb46-Cre, Myd88f/f mice. CX3CR1gfp/+ mice were kindly provided by Dr. David Littman (New York University School of Medicine). All animal handling and experimental procedures were approved by the Animal Studies Committee at Washington University. (Source: Experimental Hematology)
Source: Experimental Hematology - February 5, 2021 Category: Hematology Authors: Sidan Li, Juo-Chin Yao, Justin T. Li, Amy P. Schmidt, Daniel C. Link Tags: Brief Communication Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - February 1, 2021 Category: Hematology Source Type: research

Optimized clinical application of minimal residual disease in acute myeloid leukemia with RUNX1 –RUNX1T1
Acute myeloid leukemia (AML) with t(8;21)/RUNX1 –RUNX1T1 is a heterogeneous disease with different prognoses although it is stratified in the favorable risk group according to guidelines [1–3]. Minimal (measurable) residual disease (MRD) detection and monitoring are increasingly applied in clinical practice and are becoming a factor in decisi on-making for some therapeutic stratifications. MRD monitoring by quantitative reverse transcription polymerase chain reaction (qRT-PCR) is feasible, and the results are significantly associated with outcomes in AML with RUNX1–RUNX1T1 [4]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 29, 2021 Category: Hematology Authors: Hui Wei, Xueou Liu, Ying Wang, Dong Lin, Chunlin Zhou, Bingcheng Liu, Shaowei Qiu, Runxia Gu, Yan Li, Shuning Wei, Benfa Gong, Kaiqi Liu, Xiaoyuan Gong, Yuntao Liu, Guangji Zhang, Qiuyun Fang, Junping Zhang, Jingjing Jin, Yueshen Ma, Yingchang Mi, Jianxia Source Type: research

The Optimized Clinical Application of Minimal Residual Disease in Acute Myeloid Leukemia with RUNX1-RUNX1T1
Acute myeloid leukemia (AML) with t(8;21)/RUNX1-RUNX1T1 is a heterogeneous disease with different prognoses although it is stratified in the favorable risk group according to guidelines[1-3]. Minimal (measurable) residual disease (MRD) detection and monitoring is increasingly applied in clinical practice and is becoming a factor in decision-making for some therapeutic stratifications. MRD monitoring by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is feasible, and the results are significantly associated with outcomes in AML with RUNX1-RUNX1T1 [4]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 29, 2021 Category: Hematology Authors: Hui Wei, Xueou Liu, Ying Wang, Dong Lin, Chunlin Zhou, Bingcheng Liu, Shaowei Qiu, Runxia Gu, Yan Li, Shuning Wei, Benfa Gong, Kaiqi Liu, Xiaoyuan Gong, Yuntao Liu, Guangji Zhang, Qiuyun Fang, Junping Zhang, Jingjing Jin, Yueshen Ma, Yingchang Mi, Jianxia Source Type: research

Proteoglycans regulate protein tyrosine phosphatase receptor σ organization on hematopoietic stem/progenitor cells
Hematopoietic stem cell (HSC) transplantation is utilized in the curative therapy of thousands of patients with hematologic malignancies and blood dyscrasias annually [1]. In the United States, only 16% –75% of all patients who meet an indication for an allogeneic HSC transplant will have a human leukocyte antigen (HLA)–matched sibling or matched unrelated donor available [2]. In such patients, alternative donor HSC transplantation can be performed, utilizing either human cord blood or haploide ntical related donors [3–8]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 27, 2021 Category: Hematology Authors: Christina M. Termini, Amara Pang, Destiny M. Batton, John P. Chute Tags: Brief communication Source Type: research

Hematopoietic stem cell (HSC) divisional memory: The journey of mitochondrial metabolism through HSC division
Adult hematopoietic stem cells (HSCs) are at the apex of all hematopoietic cells. Being multipotent, HSCs give rise to all blood and immune lineages. HSCs are long-lived cells and reside mostly in a quiescent state. They divide infrequently to give rise to progeny that will maintain stem cell characteristics, that is, self-renewal. They also differentiate into highly proliferative progenitors that commit to mature lineage differentiation. HSCs are endowed with high regenerative potential and can sustain the production of all mature blood and immune cells for extended periods and, for this reason, have been used for clinica...
Source: Experimental Hematology - January 27, 2021 Category: Hematology Authors: Marie-Dominique Filippi Tags: Invited Perspective Source Type: research

Proteoglycans regulate protein tyrosine phosphatase receptor - sigma organization on hematopoietic stem/progenitor cells
Hematopoietic stem cell transplantation is utilized in the curative therapy of thousands of patients with hematologic malignancies and blood dyscrasias annually [1]. In the United States, only 16 – 75% of all patients who meet an indication for an allogeneic HSC transplant will have an HLA-matched sibling or matched unrelated donor available [2]. In such patients, alternative donor HSC transplantation can be performed, utilizing either human cord blood or haploidentical related donors [3-8 ]. In both cord blood transplantation and haploidentical donor transplantation, HSC dose is associated with improved outcomes, wh...
Source: Experimental Hematology - January 27, 2021 Category: Hematology Authors: Christina M. Termini, Amara Pang, Destiny M. Batton, John P. Chute Tags: Brief Communication Source Type: research

HSC divisional memory: the journey of mitochondrial metabolism through HSC division
Adult hematopoietic stem cells (HSCs) are at the apex of all hematopoietic cells. Being multipotent, HSCs give rise of all blood and immune lineages. HSCs are long-lived cells and mostly reside in a quiescent state. They divide infrequently to give rise to progeny that will maintain stem cell characteristics, i.e., self-renewal. They also differentiate into highly proliferative progenitors that commit to mature lineage differentiation. HSCs are endowed with high regenerative potential and can sustain the production of all mature blood and immune cells for extended periods of time, and for this reason have been used for cli...
Source: Experimental Hematology - January 27, 2021 Category: Hematology Authors: Marie-Dominique Filippi Tags: Perspective Source Type: research

Understanding of the crosstalk between normal residual hematopoietic stem cells and the leukemic niche in Acute Myeloid Leukemia.
The hematopoietic system comprises potent stem and progenitor cells which provide our bodies with a life-long supply of all blood cells. Hematopoietic stem cells (HSCs) are at the apex of the hematopoietic hierarchy, and reside in highly specialized niches within the bone marrow microenvironment, a diverse and complex tissue. Whilst the bone marrow tissue contains a large amount of hematopoietic cells, it also consists of non-hematopoietic components such as mesenchymal stromal cells (MSCs), and its derivatives osteoblasts, adipocytes and is highly vascularised and innervated [1 –3]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 23, 2021 Category: Hematology Authors: Antoniana Batsivari, William Grey, Prof Dominique Bonnet Tags: Perspective Source Type: research

Anti-CD117 immunotherapy to eliminate hematopoietic and leukemia stem cells
Adult hematopoiesis takes place in designated areas of the bone marrow, one of the most proliferative and metabolically active organs of the human body. The average daily output of blood cells is estimated to be in the range 4-5  × 1011 total nucleated cells (reviewed by Nombela-Arrieta and Manz) [1]. A sophisticated hierarchical arrangement relieves the rare hematopoietic stem cells (HSC) from the majority of the mitotic burden, which is carried by diverse multi-potent and lineage-restricted progenitor cells [2-8]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 20, 2021 Category: Hematology Authors: Norman F. Russkamp, Renier Myburgh, Jonathan D. Kiefer, Dario Neri, Markus G. Manz Tags: Perspective Source Type: research

Single-cell insights into the hematopoietic generation of T-lymphocyte precursors in mouse and human
T- and B-lymphocyte developmental processes have enjoyed particularly in-depth characterization [1 –6]. However, relatively little knowledge concerning T cells has been integrated into current discussions of broader hematopoietic differentiation. Most single-cell transcriptome analyses of multilineage hematopoietic stem and progenitor cells, while powerful and sophisticated [7–12], have under characterized lymphoid precursors. Cells starting the B-cell and natural killer (NK) cell programs are detected in bone marrow and are often labeled as general “lymphoid” precursors [13–15], but benchmark...
Source: Experimental Hematology - January 13, 2021 Category: Hematology Authors: Ellen V. Rothenberg Tags: Invited Review Source Type: research

Single-cell insights into the hematopoietic generation of T lymphocyte precursors in mouse and man
T and B lymphocyte developmental processes have enjoyed particularly in-depth characterization [1-6]. However, relatively little knowledge concerning T cells has been integrated into current discussions of broader hematopoietic differentiation. Most single-cell transcriptome analyses of multilineage hematopoietic stem and progenitor cells, while powerful and sophisticated [7-12], have under-characterized lymphoid precursors. Cells starting the B cell and natural killer (NK) cell programs are detected in bone marrow and are often labeled as general “lymphoid” precursors [13-15], but benchmarks for initiation of ...
Source: Experimental Hematology - January 13, 2021 Category: Hematology Authors: Ellen V. Rothenberg Source Type: research

Physical interaction between BAALC and DBN1 induces chemoresistance in leukemia
Genes involved in the regulation of hematopoietic stem cells (HSCs) are frequently mutated or aberrantly expressed in hematologic malignancies such as acute leukemia, implying the presence of molecular machinery shared between normal HSCs and leukemic cells. Among them is BAALC (brain and acute leukemia cytoplasmic), which has been identified as a leukemia-associated gene. BAALC is highly expressed in neuroectoderm-derived cells and in CD34 positive HSCs in human [1]. From reports up to present, BAALC expression levels showed a continuum ranging [2]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 13, 2021 Category: Hematology Authors: Hiroaki Maki, Akihide Yoshimi, Takashi Shimada, Shunya Arai, Fumio Nakanara, Ken Morita, Yasuhiko Kamikubo, Masaya Ikegawa, Mineo Kurokawa Tags: Brief Communication Source Type: research

Low content of clonogenic progenitors on day+18 is associated with acute graft-versus-host disease and predicts transplant-related mortality
Graft-versus-host disease (GVHD) negatively affects marrow function [1,2]. Acute GVHD (a-GVHD) is associated with delay of initial platelet recovery [3] and secondary platelet failure [4]. In an experimental model in mice, the transplantation of haploidentical parental marrow into F1 recipients led to \impairment of marrow graft function in all lineages [5]. Osteoblastic damage was evident after the first week of transplantation, and myelosuppression was evident before signs of the development of a-GVHD in other organs [5]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 11, 2021 Category: Hematology Authors: Giuseppe Milone, Paola Scir è, Maria Grazia Camuglia, Anna Triolo, Gaetano Moschetti, Maria Grazia Scuderi, Alessandra Cupri, Giulio Antonio Milone, Anna Bulla, Mary Ann Di Giorgio, Valerio Leotta, Angelo Curtopelle, Roberta Sciortino, Laura Parrinello, Source Type: research

Low content of clonogenic progenitors on day+18, is associated with acute graft versus host disease and predict transplant related mortality
Graft versus host disease (GVHD) negatively affects marrow function.1,2 Acute-GVHD (a-GVHD) is associated with the delay of initial platelets recovery3, and secondary platelets failure.4 In an experimental model in mice, the transplantation of haploidentical parental marrow in F1 recipients led to an impairment of marrow graft function in all lineages.5 Osteoblastic damage was evident after the first week of transplantation, and myelosuppression was evident before signs of the development of a-GVHD in other organs. (Source: Experimental Hematology)
Source: Experimental Hematology - January 11, 2021 Category: Hematology Authors: Giuseppe Milone, Paola Scir è, Maria Grazia Camuglia, Anna Triolo, Gaetano Moschetti, Maria Grazia Scuderi, Alessandra Cupri, Giulio Antonio Milone, Anna Bulla, Mary Ann Di Giorgio, Valerio Leotta, Angelo Curtopelle, Roberta Sciortino, Laura Parrinello, Source Type: research

Erythroid enucleation: a gateway into a “bloody” world
Erythrocytes or red blood cells (RBCs) constitute by large the predominant component of blood. RBCs are devoid of nucleus and other organelles, lack the cellular machinery needed for transcription and translation, and contain mainly hemoglobin, which binds and transports oxygen throughout the body. In humans, RBCs have a life span of ∼120 days [1] (variable in mice depending on the strains, 22 days in C57BL/6 mice), and are eventually cleared by macrophages. As a result, RBCs are constantly replenished from hematopoietic stem and progenitor cell differentiation. (Source: Experimental Hematology)
Source: Experimental Hematology - January 10, 2021 Category: Hematology Authors: Vijay Menon, Saghi Ghaffari Tags: Review article Source Type: research

Erythroid Enucleation: A gateway into a "bloody" world
Erythrocytes or red blood cells (RBCs) constitute by large the predominant component of blood. RBCs are devoid of nucleus and other organelles, lack the cellular machinery needed for transcription and translation and contain mainly hemoglobin that binds and transports oxygen throughout the body. In humans, RBCs have a life span of ∼120 days [1] [variable in mice depending on the strains, 22 days in C57BL/6 mice], and are eventually cleared by macrophages. As a result, RBCs are constantly replenished from hematopoietic stem and progenitor cell differentiation. (Source: Experimental Hematology)
Source: Experimental Hematology - January 10, 2021 Category: Hematology Authors: Vijay Menon, Saghi Ghaffari Source Type: research

Chronic lymphocytic leukemia –like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia
Several alterations have been described in T cells of patients with chronic lymphocytic leukemia (CLL), presumably a consequence of chronic exposure to tumor cells [1 –8]. Additionally, an elevated number of monocytes have been detected in peripheral blood (PB) of patients with the disease, exhibiting deregulated genes involved in phagocytosis and inflammation [9]. Serum cytokine levels have also been described to be altered in CLL [10], and increased levels of some cytokines such as CC chemokine ligand 3 (CCL3 and IL8 have been associated with a worse outcome [11,12]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 6, 2021 Category: Hematology Authors: Gonzalo Blanco, Anna Puiggros, Barbara Sherry, Lara Nonell, Xavier Calvo, Eul àlia Puigdecanet, Pui Yan Chiu, Yasmine Kieso, Gerardo Ferrer, Florencia Palacios, Magdalena Arnal, María Rodríguez-Rivera, Eva Gimeno, Eugènia Abella, Kanti R. Rai, Pau Abr Source Type: research

CLL-like monoclonal B cell lymphocytosis displays an increased inflammatory signature that is reduced in early stage chronic lymphocytic leukemia
Several alterations have been described in T cells of patients with chronic lymphocytic leukemia (CLL), presumably a consequence of chronic exposure to tumor cells [1-8]. Additionally, an elevated number of monocytes has been detected in peripheral blood (PB) of patients with the disease, displaying deregulated genes involved in phagocytosis and inflammation [9]. Serum cytokine levels have also been described to be altered in CLL [10], and increased levels of some cytokines such as CCL3 or IL8 have been associated with a worse outcome [11, 12]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 6, 2021 Category: Hematology Authors: Gonzalo Blanco, Anna Puiggros, Barbara Sherry, Lara Nonell, Xavier Calvo, Eul àlia Puigdecanet, Pui Yan Chiu, Yasmine Kieso, Gerardo Ferrer, Florencia Palacios, Magdalena Arnal, María Rodríguez-Rivera, Eva Gimeno, Eugènia Abella, Kanti R. Rai, Pau Abr Source Type: research

Cover 2: Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - January 1, 2021 Category: Hematology Source Type: research

Fetal sheep support the development of hematopoietic cells in vivo from human induced pluripotent stem cells
De novo generation of human hematopoietic stem and progenitor cells (HSPCs) with long-term engrafting capacity and multilineage differentiation potential has been a longstanding goal for both fundamental research on hematopoietic ontology and potential clinical applications [1 –4]. Multiple protocols for the production of pluripotent stem cell (PSC)–derived hematopoietic cells have been developed, including timed addition of cytokines and morphogens, co-culture with mouse stromal cells, embryoid bodies and the combination of these [5–10]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 1, 2021 Category: Hematology Authors: Tomoyuki Abe, Hideki Uosaki, Hiroaki Shibata, Hiromasa Hara, Borjigin Sarentonglaga, Yoshikazu Nagao, Yutaka Hanazono Source Type: research

Fetal sheep supports the development of hematopoietic cells in vivo from human iPSCs
De novo generation of human hematopoietic stem and progenitor cells (HSPCs) with long-term engrafting capacity and multilineage differentiation potential has been a long ‐standing goal for both fundamental researches of hematopoietic ontology and potential clinical applications [1-4]. Multiple protocols for the production of pluripotent stem cell (PSC)-derived hematopoietic cells have been developed including timed addition of cytokines and morphogens, co-culture with mouse stromal cells, embryoid bodies and the combination of these [5-10]. (Source: Experimental Hematology)
Source: Experimental Hematology - January 1, 2021 Category: Hematology Authors: Assistant Professor (Senior Lecturer) Tomoyuki Abe, Hideki Uosaki, Hiroaki Shibata, Hiromasa Hara, Borjigin Sarentonglaga, Yoshikazu Nagao, Professor Yutaka Hanazono Source Type: research

Arid2 regulates hematopoietic stem cell differentiation in normal hematopoiesis
Adult hematopoiesis originates from the hematopoietic stem cells (HSCs), which reside in the bone marrow. HSCs are multipotent, adult stem cells with the hallmark ability to self-renew and differentiate into all blood lineages. Epigenetic regulators have been reported to play important roles in HSC function, and their dysregulation leads to hematological malignancies [1]. These includes the switch/sugar nonfermenting (SWI/SNF) family of chromatin remodeling complexes [2 –4]. (Source: Experimental Hematology)
Source: Experimental Hematology - December 16, 2020 Category: Hematology Authors: Theresa Bluemn, Jesse Schmitz, Yuhong Chen, Yongwei Zheng, Yongguang Zhang, Shikan Zheng, Robert Burns, Joshua DeJong, Luke Christiansen, Jesus Izaguirre-Carbonell, Demin Wang, Nan Zhu Source Type: research

Arid2 regulates HSC differentiation in normal hematopoiesis
Adult hematopoiesis originates from the hematopoietic stem cells (HSCs) which reside in the bone marrow. HSCs are multipotent, adult stem cells with the hallmark ability to self-renew and differentiate into all blood lineages. Epigenetic regulators have been shown to play important roles in HSC function and their dysregulation leads to hematological malignancies [1]. These includes the Switch/Sugar Non-Fermenting (SWI/SNF) family of chromatin remodeling complexes [2 –4]. (Source: Experimental Hematology)
Source: Experimental Hematology - December 16, 2020 Category: Hematology Authors: Theresa Bluemn, Jesse Schmitz, Yuhong Chen, Yongwei Zheng, Yongguang Zhang, Shikan Zheng, Robert Burns, Joshua DeJong, Luke Christiansen, Jesus Izaguirre-Carbonell, Demin Wang, Nan Zhu Source Type: research

Persistent expression of microRNA-125a targets is required to induce murine hematopoietic stem cell repopulating activity
Hematopoietic stem cells (HSCs) are responsible for the lifelong reconstitution of all mature blood cells. As differentiation of these cells is nonreversible and terminal, the balance between self-renewal and differentiation of HSCs is tightly regulated to ensure proper tissue function. Proper HSC function is regulated both extrinsically by environmental factors that are secreted by the supporting cells in the bone marrow known as the stem cell niche and intrinsically by stem cell intrinsic programs. (Source: Experimental Hematology)
Source: Experimental Hematology - December 14, 2020 Category: Hematology Authors: Dani ëlle G. Luinenburg, Alexander Bak Dinitzen, Arthur Flohr Svendsen, R. Cengiz, Albertina Ausema, Ellen Weersing, Leonid Bystrykh, Gerald de Haan Source Type: research

Persistent expression of microRNA-125a is required to induce murine hematopoietic stem cell repopulating activity
Hematopoietic stem cells (HSCs) are responsible for the lifelong reconstitution of all mature blood cells. As differentiation of these cells is non-reversible and terminal, the balance between self-renewal and differentiation of HSCs is tightly regulated to ensure proper tissue function. Proper HSC function is regulated both extrinsically by environmental factors that are secreted by the supporting cells in the bone marrow known as the stem cell niche, and by stem cell intrinsic programs. One of these cell-intrinsic regulatory components that control HSC function are microRNAs (miRs). (Source: Experimental Hematology)
Source: Experimental Hematology - December 14, 2020 Category: Hematology Authors: DG Luinenburg, AB Dinitzen, A Flohr Svendsen, R Cengiz, A Ausema, E Weersing, L Bystrykh, G de Haan Source Type: research

How Hematopoietic Stem Cells Respond to Irradiation: Similarities and Differences between Low and High Doses of Ionizing Radiation
The scientific understanding of radiation effects is a constantly evolving field. However, it can sometimes be tricky to define doses of radiation, given the different units in which it can be expressed. The “absorbed dose” is expressed in Gray (Gy), while the “equivalent dose” and the “efficient dose” are expressed in Sievert (Sv). Although both correspond to the same units in the International Units System (J/kg), the relationship between these parameters implies several multiplicative fac tors taking into account the type of radiation, the organ sensitivity or the species [1]. (Source...
Source: Experimental Hematology - December 4, 2020 Category: Hematology Authors: Elia Henry, Marie-Laure Arcangeli Tags: Invited Review Source Type: research

How hematopoietic stem cells respond to irradiation: similarities and differences between low versus high doses of ionizing radiation
Scientific understanding of radiation effects is a constantly evolving field. However, it can be sometimes tricky to define doses of radiation, given the different units in which it can be expressed. The “absorbed dose” is expressed in Gray (Gy) while the “equivalent dose” and the “efficient dose” are expressed in Sievert (Sv). While they both correspond to the same units in the International Units System (J/kg), the relationship between these parameters implies several multiplicative fa ctors taking into account the type of radiation, the organ sensitivity or the species [1]. (Source: E...
Source: Experimental Hematology - December 4, 2020 Category: Hematology Authors: Elia Henry, Marie-Laure Arcangeli Source Type: research

Engineering human hematopoietic environments through ossicle and bioreactor technologies exploitation
Hematopoietic stem and progenitor cells (HSPCs), primarily residing within the bone marrow (BM), sustain life-long hematopoiesis1-4. The BM microenvironment is composed of a range of cell types – from mesenchymal stromal cells (MSCs) and endothelium to various mature hematopoietic cell types – and provide various supportive extrinsic cues5, 6. The accumulation of somatic mutations within HSPCs is well described as driver of a range of hematological disorders such as myelodysplastic syn dromes (MDS), myeloproliferative neoplasms (MPNs), and leukemias7-12. (Source: Experimental Hematology)
Source: Experimental Hematology - December 2, 2020 Category: Hematology Authors: Pia Sommerkamp, Fran çois E. Mercier, Adam C. Wilkinson, Dominique Bonnet, Paul E. Bourgine Tags: Review Source Type: research

AMD3100 redosing fails to repeatedly mobilize hematopoietic stem cells in the nonhuman primate and humanized mouse
Hematopoietic stem and progenitor cell (HSPC) transplantation constitutes the gold standard treatment for many malignant and nonmalignant conditions [1]. Mobilization of HSPCs from the bone marrow (BM) niche into the peripheral blood (PB) circulation is a critical part of most autologous and allogeneic HSPC transplant protocols, facilitating HSPC collection from the circulation by apheresis [2,3]. This avoids invasive BM harvest, with inherent risks of infection, bleeding, structural damage, and the need for a general anesthetic [4,5]. (Source: Experimental Hematology)
Source: Experimental Hematology - December 1, 2020 Category: Hematology Authors: Clare Samuelson, Stefan Radtke, Margaret Cui, Anai Perez, Hans-Peter Kiem, Olivier Humbert Source Type: research

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

Salvianolic acid A inhibits the growth of diffuse large B-cell lymphoma through MAPK pathways
Diffuse large B-cell lymphoma (DLBCL), an immense heterogeneous disease, can be categorized into two major molecular subtypes termed germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL [1]. This molecular distinction represents lymphomas derivating from different stages of B cell differentiation, and reflects fairly different intracellular oncogenic pathways for pathogenesis [2-4]. Although the combinatorial chemotherapy R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone) makes the majority of patients curable [5], a subset exhibits severe side effects or relapses after in...
Source: Experimental Hematology - December 1, 2020 Category: Hematology Authors: Shuting Li, Jingwen Fang, Ting Si, Ying Lu, Lei Jiang Source Type: research

AMD3100 re-dosing fails to repeatedly mobilize hematopoietic stem cells in the non-human primate and humanized mouse
Hematopoietic stem and progenitor cell (HSPC) transplantation constitutes the gold standard treatment for many malignant and non-malignant conditions. 1 Mobilization of HSPCs from the bone marrow (BM) niche into the peripheral blood (PB) circulation is a critical part of most autologous and allogeneic HSPC transplant protocols, facilitating HSPC collection from the circulation by apheresis.2,3 This avoids invasive BM harvest, with inherent risks of infection, bleeding, structural damage, and the need for a general anaesthetic. (Source: Experimental Hematology)
Source: Experimental Hematology - December 1, 2020 Category: Hematology Authors: Clare Samuelson, Stefan Radtke, Margaret Cui, Anai Perez, Hans-Peter Kiem, Olivier Humbert Source Type: research

Overlooking the obvious? On the potential of treatment alterations to predict patient-specific therapy response
Within this perspective article we summarize the conceptual idea of using dynamic information to obtain a better understanding of complex pathophysiological processes within their particular “host environment”, which also allows to intrinsically map patient-specific heterogeneity. Specifically, we discuss to which extend treatment alterations can provide additional information to understand a patient's individual condition and use this information to further adapt the therapeutic st rategy. This conceptual discussion is illustrated by using examples from myeloid leukemias for which we recently applied this conc...
Source: Experimental Hematology - November 23, 2020 Category: Hematology Authors: Ingo Roeder, Ingmar Glauche Tags: Perspective Source Type: research

The RUNX1/RUNX1T1 Network: Translating Insights into Therapeutic Options
Fusion genes and their underlying chromosomal alterations are a hallmark of acute myeloid leukaemia (AML). They are particularly prevalent in paediatric AML where more than 50% of all cases harbour a fusion gene [1, 2]. As fusion genes predict clinical outcome they are used for patient stratification in the WHO 2016 classification of AML [3]. More than 60% of all rearrangements found in pediatric AML target only five different protein complexes: the core binding factor (CBF), the epigenetic regulator MLL, the nuclear receptor RARA and the nuclear pore component NUP98 [1, 2]. (Source: Experimental Hematology)
Source: Experimental Hematology - November 16, 2020 Category: Hematology Authors: Laura E. Swart, Olaf Heidenreich Tags: Review Source Type: research

Corrigendum to “AC220 and AraC cause differential inhibitory dynamics in patient-derived M5-AML with FLT3-ITD and, thus, ultimately distinct therapeutic outcomes” [Experimental Hematology 2017;45:36–44]
The affiliation given for Xiaoyu An, one of the authors of the paper entitled “AC220 and AraC cause differential inhibitory dynamics in patient-derived M5-AML with FLT3-ITD and, thus, ultimately distinct therapeutic outcomes" was incorrectly stated as Crown Bioscience and should have been State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, Chin a. (Source: Experimental Hematology)
Source: Experimental Hematology - November 13, 2020 Category: Hematology Authors: Xiaoyu An, Jinping Liu, Na Wang, Di Wang, Liang Huang, Likun Zhang, Jie Cai, Jean-Pierre Wery, Demin Zhou, Jianfeng Zhou, Qi-Xiang Li Tags: Erratum Source Type: research

Beyond “to divide or not to divide”: Kinetics matters in hematopoietic stem cells
A trillion blood cells are produced daily to maintain blood function at steady state. This immense regenerative output is achieved by the concerted action of rare and infrequently dividing hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). Decades of work, primarily in mouse models, have built complex roadmaps of the first steps of hematopoiesis by dissecting the cascade of cell divisions occurring from the most potent HSCs to multilineage and, in turn, unilineage progenitors. Recently, single-cell RNA-seq and clonal tracking have complemented these by defining differentiation trajectories at single-cell r...
Source: Experimental Hematology - November 11, 2020 Category: Hematology Authors: Carys Johnson, Serena Belluschi, Elisa Laurenti Tags: Perspective Source Type: research

Beyond “to divide or not to divide”: kinetics matter in Haematopoietic Stem Cells
A trillion blood cells are produced daily to maintain blood function at steady state. This immense regenerative output is achieved by the concerted action of rare and infrequently dividing hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). Decades of work, primarily from mouse models, have built complex roadmaps of the first steps of hematopoiesis by dissecting the cascade of cell divisions occurring from the most potent HSCs to multi- and in turn unilineage progenitors. Recently, single cell RNA-seq and clonal tracking have complemented these by defining differentiation trajectories at single cell resolut...
Source: Experimental Hematology - November 11, 2020 Category: Hematology Authors: Carys Johnson, Serena Belluschi, Elisa Laurenti Tags: Perspective Source Type: research

Generation of a lenalidomide-sensitive syngeneic murine in vivo multiple myeloma model by expression of CrbnI391V
Multiple myeloma is a genetically heterogeneous malignancy of plasma cells. Current treatments for multiple myeloma comprise proteasome inhibitors, steroids, chemotherapy, antibodies and immunomodulatory drugs (IMiDs) 1-3. However, despite combination of these drugs, multiple myeloma remains incurable in the majority of cases. (Source: Experimental Hematology)
Source: Experimental Hematology - November 10, 2020 Category: Hematology Authors: Linda R öhner, Yuen Lam Dora Ng, Annika Scheffold, Stefanie Lindner, Simon Köpff, Andreas Brandl, Andreas Beilhack, Jan Krönke Source Type: research

Transplantation of T-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates
Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers a potential cure for patients with blood cancers and HIV infection. The curative effect of alloHSCT in these conditions is attributed to alloimmune responses directed against tumor cells, or cells harboring an HIV reservoir (graft-versus-host effect [GvHE]) [1,2]. However, alloHSCT is commonly associated with alloimmune responses to healthy tissues causing graft-versus-host disease (GvHD), which remains one of the major causes of morbidity and mortality [3]. (Source: Experimental Hematology)
Source: Experimental Hematology - November 8, 2020 Category: Hematology Authors: Saritha S. D'Souza, Sarah Bennett, Akhilesh Kumar, Laurel E. Kelnhofer, Jason Weinfurter, Kran Suknuntha, Jennifer Coonen, Andres Mejia, Heather Simmons, Thaddeus Golos, Peiman Hematti, Christian M. Capitini, Matthew R. Reynolds, Igor I. Slukvin Source Type: research

Transplantation of TCR α/β-depleted allogeneic bone marrow in nonhuman primates
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for hematologic cancers and chronic infections such as HIV. Its success in these settings is attributed to the ability of engrafting immune cells to eliminate cancer cells or deplete HIV reservoir (graft-versus-host effect; GvHE). However, alloHSCT is commonly associated with graft-versus-host diseases (GvHD) causing significant morbidity and mortality, thereby requiring development of novel allogeneic HSCT protocols and therapies promoting GvHE without GvHD using physiologically relevant preclinical models. (Source: Experimental Hematology)
Source: Experimental Hematology - November 8, 2020 Category: Hematology Authors: Saritha S. D'Souza, Sarah Bennett, Akhilesh Kumar, Laurel E. Kelnhofer, Jason Weinfurter, Kran Suknuntha, Jennifer Coonen, Andres Mejia, Heather Simmons, Thaddeus Golos, Peiman Hematti, Christian M. Capitini, Matthew R. Reynolds, Igor I. Slukvin Source Type: research