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Q A Hill, L C Harrison, A D Padmakumar, R G Owen, K R Prasad, G F Lucas, P Tachtatzis
OBJECTIVE AND IMPORTANCE: Transplantation-mediated alloimmune thrombocytopenia (TMAT) occurs when leukocytes transferred in a donor organ from a patient with immune thrombocytopenia (ITP), mount a response against recipient platelets. We present the first fatal case of TMAT following liver transplantation and review its aetiology and treatment. CLINICAL PRESENTATION: The liver donor had ITP and died from an intracranial haemorrhage. The recipient platelet count fell to 2 × 10(9)/l on post-operative day 2...
October 21, 2016: Hematology (Amsterdam, Netherlands)
Jennifer E Adair, Timothy Waters, Kevin G Haworth, Sara P Kubek, Grant D Trobridge, Jonah D Hocum, Shelly Heimfeld, Hans-Peter Kiem
Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34(+) blood cell products for transplantation...
October 20, 2016: Nature Communications
Suchismita Daw, Ritam Chatterjee, Aditya Law, Sujata Law
Hematological disorders like myelodysplastic syndrome (MDS) may arise due to cumulative dysregulation of various signalling pathways controlling proliferation, differentiation, maturation and apoptosis of bone marrow cells. This devastating bone marrow condition can be due to consequential abnormalities in haematopoiesis as well as its supportive microenvironment. Although mutations related to JAK/STAT pathway are common in myeloproliferative neoplasms, further studies are required to fully explore the myelodysplastic scenario regarding the concerned pathway...
October 7, 2016: Chemico-biological Interactions
June Baik, Alessandro Magli, Naoyuki Tahara, Scott A Swanson, Naoko Koyano-Nakagawa, Luciene Borges, Ron Stewart, Daniel J Garry, Yasuhiko Kawakami, James A Thomson, Rita C R Perlingeiro
Mechanisms of haematopoietic and cardiac patterning remain poorly understood. Here we show that the BMP and Wnt signalling pathways are integrated in an endoglin (Eng)-dependent manner in cardiac and haematopoietic lineage specification. Eng is expressed in early mesoderm and marks both haematopoietic and cardiac progenitors. In the absence of Eng, yolk sacs inappropriately express the cardiac marker, Nkx2.5. Conversely, high levels of Eng in vitro and in vivo increase haematopoiesis and inhibit cardiogenesis...
October 7, 2016: Nature Communications
Adam L MacLean, Cristina Lo Celso, Michael Ph Stumpf
Stem cells are fundamental to human life and offer great therapeutic potential, yet their biology remains incompletely - or in cases even poorly - understood. The field of stem cell biology has grown substantially in recent years due to a combination of experimental and theoretical contributions: the experimental branch of this work provides data in an ever-increasing number of dimensions, while the theoretical branch seeks to determine suitable models of the fundamental stem cell processes that these data describe...
September 27, 2016: Stem Cells
Monika Holubova, Michaela Miklikova, Martin Leba, Daniel Georgiev, Pavel Jindra, Martin Caprnda, Rachele Ciccocioppo, Peter Kruzliak, Daniel Lysak
BACKGROUND: Leukaemia is an aggressive cancer of haematopoiesis. Despite increasing treatment success, the relapse rate is still high. Natural killer (NK) cells play a key role in the immune response to malignancies; thus, it is conceivable that NK cell-based immunotherapy may control relapses, while extending the disease-free survival. In our study, we investigated whether cryopreserved NK cells are able to kill the leukaemic K562 cell line, the necessity of IL-2 co-application and the association of activation marker expression (NKp44, NKG2D and CD25) with cytotoxic potential...
September 10, 2016: Journal of Cancer Research and Clinical Oncology
Ashwin Unnikrishnan, Yi F Guan, Yizhou Huang, Dominik Beck, Julie A I Thoms, Sofie Peirs, Kathy Knezevic, Shiyong Ma, Inge V de Walle, Ineke de Jong, Zara Ali, Ling Zhong, Mark J Raftery, Tom Taghon, Jonas Larsson, Karen L MacKenzie, Pieter V Vlierberghe, Jason W H Wong, John E Pimanda
Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells...
September 6, 2016: Nucleic Acids Research
Andrew L Young, Grant A Challen, Brenda M Birmann, Todd E Druley
Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones->0.02 variant allele fraction (VAF)-due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0...
2016: Nature Communications
Christin Kretzschmar, Catrin Roolf, Katrin Timmer, Anett Sekora, Gudrun Knübel, Hugo Murua Escobar, Robert Jaster, Sarah Müller, Georg Fuellen, Rüdiger Köhling, Christian Junghanss
Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ROS on hematopoiesis during aging has not yet been investigated. In this study, UCP2 knockout mice were analyzed at aging stages of 3, 12, and 24 months with respect to oxidative and energy status of bone marrow cells...
August 17, 2016: Experimental Hematology
Concetta Saponaro, Michele Maffia, Nicola Di Renzo, Addolorata Maria Luce Coluccia
Chronic Myelogenous Leukemia (CML)-initiating cells (CICs) express the hybrid oncoprotein BCR-ABL at the highest levels compared to their differentiated progeny but fail to expand at the same rate as downstream leukemic myeloid cells. Moreover, the primitive stem cell clone that originates the indolent CML chronic phase (CP) remains almost invariant as the disease evolves to a fatal blast crisis (BC). Compared to their healthy counterpart, the most dormant BCR-ABL+ CICs show the tendency to remain in a somewhat unusual 'proliferative quiescence', i...
August 17, 2016: Current Drug Targets
Neha Bhatnagar, Laure Nizery, Oliver Tunstall, Paresh Vyas, Irene Roberts
Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is preceded by a transient neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in the key haematopoietic transcription factor gene GATA1. These mutations are found in almost one third of DS neonates and are frequently clinically and haematologcially 'silent'...
October 2016: Current Hematologic Malignancy Reports
Wenyuan Wang, Tonis Org, Amélie Montel-Hagen, Peter D Pioli, Dan Duan, Edo Israely, Daniel Malkin, Trent Su, Johanna Flach, Siavash K Kurdistani, Robert H Schiestl, Hanna K A Mikkola
DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection...
2016: Nature Communications
Bembem Khuraijam, Parul Sobti, Darilin Shangpliang, Nita Khurana
Pilomatricoma is a benign follicular skin appendage tumour. It usually occurs as solitary lesion and is most commonly seen in the face and upper extremeties. Here we report a rare case of extramedullary haematopoiesis (EMH) in pilomatricoma in a 38-year-old lady.
June 2016: Journal of Clinical and Diagnostic Research: JCDR
Lucas Waltzer, Laetitia Bataillé, Sandrine Peyrefitte, Marc Haenlin
No abstract text is available yet for this article.
March 1, 2016: EMBO Journal
Lisa Judith Crawford, Alexandra Elizabeth Irvine
Haematopoiesis is the term used to describe the production of blood cells. This is a tightly regulated hierarchical system in which mature circulating blood cells develop from a small population of haematopoietic stem (HSC) and progenitor cells within the microenvironment of the bone marrow. Molecular and genetic abnormalities arising in these stem cells lead to a block in the normal programme of proliferation and differentiation and result in the development of the blood cancers known as the leukaemias and lymphomas...
September 2016: Journal of Cell Communication and Signaling
Tomer Itkin, Shiri Gur-Cohen, Joel A Spencer, Amir Schajnovitz, Saravana K Ramasamy, Anjali P Kusumbe, Guy Ledergor, Yookyung Jung, Idan Milo, Michael G Poulos, Alexander Kalinkovich, Aya Ludin, Karin Golan, Eman Khatib, Anju Kumari, Orit Kollet, Guy Shakhar, Jason M Butler, Shahin Rafii, Ralf H Adams, David T Scadden, Charles P Lin, Tsvee Lapidot
No abstract text is available yet for this article.
July 20, 2016: Nature
Roshana Thambyrajah, Deniz Ucanok, Maryam Jalali, Yasmin Hough, Robert Neil Wilkinson, Kathryn McMahon, Chris Moore, Martin Gering
A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity...
September 1, 2016: Developmental Biology
M Miarons, M Velasco, L Campins, S Fernández, T Gurrera, L Lopez-Viaplana
WHAT IS KNOWN AND OBJECTIVE: Unexplained thrombocytopenia is a common clinical problem, and the possibility of drug-induced thrombocytopenia must be considered. Moreover, chemotherapy agents are known to typically cause thrombocytopenia by suppressing haematopoiesis, but they can also cause immune thrombocytopenia in which the mechanism involves antibody-mediated platelet destruction. CASE DESCRIPTION: We report a case of severe thrombocytopenia related to trastuzumab administration in which the patient exhibits a slow drift downward in platelet counts with repeated cycles of trastuzumab...
October 2016: Journal of Clinical Pharmacy and Therapeutics
Sara Cuvertino, Georges Lacaud, Valerie Kouskoff
During embryogenesis, the three SOXF transcription factors, SOX7, SOX17 and SOX18, regulate the specification of the cardiovascular system and are also involved in the development of haematopoiesis. The ectopic expression of SOX17 in both embryonic and adult blood cells enhances self-renewal. Likewise, the enforced expression of SOX7 during embryonic development promotes the proliferation of early blood progenitors and blocks lineage commitment. However, whether SOX7 expression can also affect the self-renewal of adult blood progenitors has never been explored...
July 2016: Open Biology
Sven Reischauer, Oliver A Stone, Alethia Villasenor, Neil Chi, Suk-Won Jin, Marcel Martin, Miler T Lee, Nana Fukuda, Michele Marass, Alec Witty, Ian Fiddes, Taiyi Kuo, Won-Suk Chung, Sherveen Salek, Robert Lerrigo, Jessica Alsiö, Shujun Luo, Dominika Tworus, Sruthy M Augustine, Sophie Mucenieks, Björn Nystedt, Antonio J Giraldez, Gary P Schroth, Olov Andersson, Didier Y R Stainier
Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers. Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location...
July 14, 2016: Nature
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