Forged in the fire: Lasting impacts of inflammation on hematopoietic progenitors
Hematopoietic stem and progenitor cells (HSPCs) are multipotent and regenerative cells within the bone marrow that support the lifelong production of all the cells of the blood and immune systems. Historically thought to be a quiescent and rather inert cell type, recent studies have shown that hematopoietic stem cells (HSCs) respond to inflammatory stimuli, and these responses have a long-term impact on the overall size and composition of the HSC pool. Naturally occurring genetically variant HSC clones show differential responses to inflammatory stimuli that can influence clonal competition and contribute to clonal hematop...
Source: Experimental Hematology - April 3, 2024 Category: Hematology Authors: Ruoqiong Cao, Apoorva Thatavarty, Katherine Y. King Tags: Review Source Type: research
Lethal and sublethal effects of programmed cell death pathways on hematopoietic stem cells
In multicellular organisms, the capacity of cells to commit suicide is critical to maintain homeostasis in high turnover tissues. In young adult humans, around 4 million cells are estimated to turn over every second, about 90% of which are of hematopoietic origin [1]. Based on a mathematical analysis that integrates ubiquity, mass, and lifespan of all major cell types in a human body, approximately 2 ×1011 red blood cells, 6×1010 neutrophils, 5×109 B cells, 2×109 T cells, and 1×1011 platelets are predicted to be generated every day, but our remarkably constant blood cell counts indicate that the same number of cells a...
Source: Experimental Hematology - April 3, 2024 Category: Hematology Authors: Yuta Yamada, Zhiqian Zheng, Alaa K. Jad, Masayuki Yamashita Tags: Review Source Type: research
Chromatin Organization in Myelodysplastic Syndrome
Myelodysplastic syndrome (MDS) is a heterogenous group of pre-leukemic myeloid malignancies involving ineffective hematopoiesis, morphological bone marrow abnormalities, and increased risk of transformation to acute myeloid leukemia (AML) [1, 2]. At current, morphological examinations of bone marrow cells and peripheral blood counts serve as the primary diagnostic and surveillance tools for MDS patients. While classically observed cytogenetic abnormalities can be pathognomonic in establishing the clonal nature of the disease, mutational abnormalities only play a supportive role in the diagnosis and management of MDS [3]. (...
Source: Experimental Hematology - April 3, 2024 Category: Hematology Authors: Jane Jialu Xu, Aaron D. Viny Tags: Review Source Type: research
Forged in the Fire: Lasting Impacts of Inflammation on Hematopoietic Progenitors.
Quiescence and differentiation of hematopoietic stem and progenitor cells (HSPC) can be modified by systemic inflammatory cues. Such cues can not only yield short term changes in HSPCs such as in supporting emergency granulopoiesis but can also promote lasting influences on the HSPC compartment. First, inflammation can be a driver for clonal expansion, promoting clonal hematopoiesis for certain mutant clones, reducing overall clonal diversity, and reshaping the composition of the HSPC pool with significant health consequences. (Source: Experimental Hematology)
Source: Experimental Hematology - April 3, 2024 Category: Hematology Authors: Ruoqiong Cao, Apoorva Thatavarty, Katherine Y. King Tags: Review Source Type: research
Remembering Professor Connie Eaves: an exceptional researcher, mentor and friend
On March 7, 2024, the Experimental Hematology community lost a legend. Editor of our journal (2017- June 2023), and a member of the International Society for Experimental Hematology (ISEH) for over 50 years, Professor Connie Eaves was thoroughly devoted to ISEH and its community of researchers. She contributed significantly to the ISEH leadership, notably as President (2002-2003) and was the highly deserving recipient of both the Donald Metcalf Award (2008) and the Outstanding Mentor award (2023). (Source: Experimental Hematology)
Source: Experimental Hematology - March 28, 2024 Category: Hematology Authors: David Kent, Louise E. Purton Tags: Obituary Source Type: research
IFC Editorial Board
(Source: Experimental Hematology)
Source: Experimental Hematology - March 27, 2024 Category: Hematology Source Type: research
The critical role of the bone marrow stromal microenvironment for the development of drug screening platforms in leukemia
High-throughput screening has revolutionized drug development and monumentally decreased the costs associated with testing compound libraries [1]. Despite such advances, there has been little change in the success rate of commercial drug development for novel therapies [1,2]. Although the use of tumor cell monocultures in high-throughput drug screening has been used as the conventional platform for identifying new treatments for leukemia [3], novel cancer therapeutics displaying seemingly promising in vitro efficacy from such drug screening platforms often fail to translate their expected advantages [4,5]. (Source: Experimental Hematology)
Source: Experimental Hematology - March 27, 2024 Category: Hematology Authors: Rhiannon G. Panting, Rishi S. Kotecha, Laurence C. Cheung Tags: Review Article Source Type: research
The critical role of the bone marrow stromal microenvironment for development of drug screening platforms in leukemia
High-throughput screening has revolutionized drug development and monumentally decreased the costs associated with testing compound libraries (1). Despite such advances, there has been little change in the success rate of commercial drug development of novel therapies (1,2). While the use of tumor cell monocultures in high-throughput drug screening has been used as the conventional platform for identifying new treatments for leukemia (3), novel cancer therapeutics displaying seemingly promising in vitro efficacy from such drug screening platforms often fail to translate their expected advantages (4,5). (Source: Experimental Hematology)
Source: Experimental Hematology - March 27, 2024 Category: Hematology Authors: Rhiannon G. Panting, Rishi S. Kotecha, Laurence C. Cheung Tags: Review Source Type: research
Relative impact of THPO mutation causing hereditary thrombocythemia
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that is characterized by sustained proliferation of megakaryocytes and thrombocytosis. An elevated platelet count results in thrombotic or hemorrhagic episodes. ET occasionally causes leukemic transformation or myelofibrosis. Somatic mutations of JAK2, MPL, and CALR are frequently observed in cases of ET. Hereditary thrombocythemia (HT) is an autosomal-dominant disorder and its clinical features resemble those of sporadic ET. (Source: Experimental Hematology)
Source: Experimental Hematology - March 26, 2024 Category: Hematology Authors: Hiroyuki Kimura, Masahiro Onozawa, Toshihiro Matsukawa, Hideki Goto, Takeshi Kondo, Takanori Teshima Tags: Brief Communication Source Type: research
Gut Microbial Dysbiosis in the Pathogenesis of Leukemia: An Immune-based Perspective
A growing body of evidence points to the role of various human gut microbes in the genesis and progression of different cancers and hematological diseases including leukemia. This is carried out by both direct and indirect mechanisms [1]. For example, the bacterial species of Fusobacterium nucleatum directly binds to E-cadherin through its adhesin factor FadA (Fusobacterium adhesin A) thereby triggering the process of tumorigenesis in colorectal cancer [2]. Indirectly, the gut microbiota, with its constant provocation of the immune system, may lead into the development of cancer by creating a pro-inflammatory state within ...
Source: Experimental Hematology - March 23, 2024 Category: Hematology Authors: Mayuri Goswami, Purabi Deka Bose Tags: Review Source Type: research
Assessment of a novel NRAS in-frame tandem duplication causing a myelodysplastic/myeloproliferative neoplasm
Myelodysplastic and myeloproliferative neoplasms (MDS/MPNs) are a group of heterogeneous clonal hematological diseases with overlapping clinical, genetic, and morphological myelodysplastic and myeloproliferative features1 –3. MDS/MPNs of childhood are rare with juvenile myelomonocytic leukemia (JMML) being best described1,4. Clinical signs of JMML include hepatosplenomegaly, and infiltrations of skin, gut and lung4. Peripheral blood shows leukocytosis with monocytosis and myeloid precursors, thrombocytopenia and an emia5. (Source: Experimental Hematology)
Source: Experimental Hematology - March 22, 2024 Category: Hematology Authors: Cora C.A. Beckmann, Senthilkumar Ramamoorthy, Eirini Trompouki, Wolfgang Driever, Stephan Schwarz-Furlan, Brigitte Strahm, Ayami Yoshimi, Charlotte M. Niemeyer, Miriam Erlacher, Friedrich G. Kapp Tags: Article Source Type: research
Identification of Red blood cell distribution width as a prognostic factor in acute myeloid leukemia
Acute myeloid leukemia (AML) is a heterogeneous clonal disease of the myeloid malignancies with poor outcomes. (1,2) Newly diagnosed patients with AML can be stratified by cytogenetic and molecular abnormalities into favorable, intermediate and adverse-risk categories to receive different treatment strategies. (3,4) Based on previous literature many other clinical features such as age, white blood cell counts (WBC) at diagnosis, lactate dehydrogenase (LDH), et al have been identified as prognostic parameters of AML. (Source: Experimental Hematology)
Source: Experimental Hematology - March 18, 2024 Category: Hematology Authors: Qiaoxue Liu, Yujia Zhai, Yan Hui, Jiayuan Chen, Yingchang Mi, Jianxiang Wang, Hui Wei Tags: Article Source Type: research
Abcb10 regulates murine hematopoietic stem cell potential and erythroid differentiation
Erythrocytes, produced in the bone marrow (BM) are the most abundantly produced cells within the body (Hatton et al., 2023). Hematopoietic stem cells (HSC) in the BM are essential for life-long hematopoiesis and are the origin of all erythrocytes (Orkin and Zon, 2008). Although physiological HSCs rarely divide and are cell cycle quiescent (Trumpp et al., 2010) (Wilson et al., 2008), their proliferation and multilineage differentiation also substantiates native adult hematopoiesis (Morcos et al., 2020) (S äwen et al., 2018). (Source: Experimental Hematology)
Source: Experimental Hematology - March 15, 2024 Category: Hematology Authors: Ayano Yahagi, Makiko Mochizuki-Kashio, Yuriko Sorimachi, Keiyo Takubo, Ayako Nakamura-Ishizu Tags: Article Source Type: research
Depletion of Ppp6c in hematopoietic and vascular endothelial cells causes embryonic lethality and decreased hematopoietic potential
Protein phosphatase 6 (PP6) is a Ser/Thr protein phosphatase composed of three subunits: the catalytic subunit Ppp6c and the regulatory subunits Ankrds and SAPS [1]. The diverse phenotypes observed following siRNA-based knockdown of Ppp6c in cultured mammalian cells suggest that PP6 plays roles in cell growth and DNA repair [2-4]. There is also evidence that PP6 regulates NF- κB signaling [5] and mitogen-activated protein kinases (MAPKs) [6, 7] and inactivates TAK1 [8]. Studies in flies indicate that depletion of PpV, a homolog of Ppp6c, results in a cell growth defect [9], suggesting that Ppp6c promotes cell growth. (Sou...
Source: Experimental Hematology - March 13, 2024 Category: Hematology Authors: Ayumi Kondo, Hirokazu Tanaka, Shinya Rai, Hiroshi Shima, Itaru Matsumura, Toshio Watanabe Tags: Article Source Type: research
Biomaterial-assisted therapeutic cell production and modification in vivo
Hematopoietic stem cell transplantation remains the preferred treatment for a variety of hematopoietic function disorders. To address the issue of limited numbers of hematopoietic stem/progenitor cells (HSPCs), significant progress has been made in the technology for ex vivo expansion of HSPCs. In addition, biomaterial-assisted in vivo production technology for therapeutic cells, including HSPCs, is gradually gaining attention. With the aid of specifically functional biomaterials, researchers can construct bone-like tissues exhibiting typical bone marrow-like structures (termed in vivo osteo-organoids in this article) for ...
Source: Experimental Hematology - March 1, 2024 Category: Hematology Authors: Kai Dai, Jing Wang, Changsheng Liu Source Type: research
