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https://www.readbyqxmd.com/read/29346763/derepression-of-the-iroquois-homeodomain-transcription-factor-gene-irx3-confers-differentiation-block-in-acute-leukemia
#1
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29343582/hiv-replication-and-latency-in-a-humanized-nsg-mouse-model-during-suppressive-oral-combinational-art
#2
Sangeetha Satheesan, Haitang Li, John C Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W Synold, John J Rossi, Jiehua Zhou
Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, they cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29339402/canonical-notch-signaling-is-dispensible-for-adult-steady-state-and-stress-myelo-erythropoiesis
#3
Sara Duarte, Petter S Woll, Natalija Buza-Vidas, Desmond Wai Loon Chin, Hanane Boukarabila, Tiago C Luís, Laura Stenson, Tiphaine Bouriez-Jones, Helen Ferry, Adam J Mead, Deborah Atkinson, Shaobo Jin, Sally-Ann Clark, Bishan Wu, Emmanouela Repapi, Nicki Gray, Stephen Taylor, Anders P Mutvei, Yat Long Tsoi, Claus Nerlov, Urban Lendahl, Sten Eirik W Jacobsen
While an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29338084/importance-of-b-cells-to-development-of-tregs-and-prolongation-of-tissue-allograft-survival-in-recipients-receiving-autologous-bone-marrow-transplantation
#4
Reginald M Gorczynski, Kaveh Farrokhi, Christopher Gorczynski, Hassan Sadozai, Fang Zhu, Ismat Khatri
We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased Tregs of both host and bone marrow donor origin. Regulatory B cells (Bregs) can also modulate T cell immunity and B cells may be implicated in the development of Tregs. Accordingly, we explored the effect of B cell depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received BALB/c skin allografts followed 7d later by myeloablation using cyclophosphamide and busulphan...
January 16, 2018: Immunology
https://www.readbyqxmd.com/read/29337025/hepatosplenic-t-cell-lymphoma-a-review-of-clinicopathologic-features-pathogenesis-and-prognostic-factors
#5
Mariko Yabe, Roberto N Miranda, L Jeffrey Medeiros
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that arises most often in adolescents and young adults. Patients with HSTCL commonly present with B-symptoms and cytopenias which may suggest a diagnosis of acute leukemia initially. Patients present with extranodal disease involving the spleen, liver and bone marrow; lymphadenopathy is usually absent. The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage, often negative for CD4 and CD8 and positive for T-cell receptor γδ or, less often, αβ...
January 11, 2018: Human Pathology
https://www.readbyqxmd.com/read/29335601/loss-of-cd14-leads-to-disturbed-epithelial-b-cell-crosstalk-and-impairment-of-the-intestinal-barrier-after-e-coli-nissle-monoassociation
#6
Marijana Basic, Manuela Buettner, Lydia M Keubler, Anna Smoczek, Inga Bruesch, Stephanie Buchheister, André Bleich
The TLR4 co-receptor CD14 was identified as an IBD candidate gene. Here, its influence on the intestinal barrier was addressed utilizing E. coli Nissle (EcN), which induces severe inflammation in germfree TLR4-/- mice. After monoassociation, EcN was detected in spleens and livers of TLR4-/- and CD14-/- but not wildtype mice. Barrier impairment was characterized by increased apoptosis and decreased epithelial junction (EJ) expression and was reversed by TLR2 stimulation in CD14-/- mice. Bone marrow (BM) transplantation revealed contribution of hematopoietic and non-hematopoietic cells towards intestinal homeostasis...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335408/escape-from-thymic-deletion-and-anti-leukemic-effects-of-t-cells-specific-for-hematopoietic-cell-restricted-antigen
#7
Ji-Min Ju, Min Ho Jung, Giri Nam, Woojin Kim, Sehwa Oh, Hyun Duk Kim, Joo Young Kim, Jun Chang, Sung Hak Lee, Gyeong Sin Park, Chang-Ki Min, Dong-Sup Lee, Moon Gyo Kim, Kyungho Choi, Eun Young Choi
Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT)...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334367/unmanipulated-haploidentical-transplantation-conditioning-with-busulfan-cyclophosphamide-and-anti-thymoglobulin-for-adult-severe-aplastic-anaemia
#8
L-P Xu, Z-L Xu, F-R Wang, X-D Mo, T-T Han, W Han, Y-H Chen, Y-Y Zhang, J-Z Wang, Y Wang, C-H Yan, Y-Q Sun, F-F Tang, X-H Zhang, X-J Huang
We conducted a retrospective analysis to evaluate outcomes of haploidentical transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults received haploidentical transplantation between May 2011 and December 2016. Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti-thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and peripheral blood transplantation. The patients' median age was 25 years. Forty-nine patients survived for more than 28 days and all achieved donor myeloid engraftment...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29331844/assessing-the-risk-of-cmv-reactivation-and-reconstitution-of-antiviral-immune-response-post-bone-marrow-transplantation-by-the-quantiferon-cmv-assay-and-real-time-pcr
#9
Adalbert Krawczyk, Jessica Ackermann, Birgit Goitowski, Rudolf Trenschel, Markus Ditschkowski, Jörg Timm, Hellmut Ottinger, Dietrich W Beelen, Nico Grüner, Melanie Fiedler
BACKGROUND: CMV reactivation is a major cause of severe complications in allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R). The reconstitution of CMV-specific T-cell responses after transplantation is crucial for the control of CMV reactivation. OBJECTIVES: The study aimed to determine the cellular immune status correlating with protection from high-level CMV viremia (>5000 copies/ml) and disease...
January 9, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29325312/-outcomes-of-alternative-donor-allogeneic-hematopoietic-stem-cell-transplantation-for-fanconi-anemia-a-five-cases-report
#10
W J Wang, Y Q Sun, F F Tang, T T Han, X D Mo, J Z Wang, X H Zhang, X J Huang, L P Xu
Five patients with Fanconi anemia who received hematopoietic cell transplantation were retrospectively analyzed. The conditioning regimens included fludarabine, cyclophosphamide and anti-thymocyte globulin. Two patients received both bone marrow and peripheral blood stem cells as the source of stem cell grafts from haploidentical matched related donors, while the others received peripheral blood stem cells from unrelated donors. All patients tolerated well and reached hematopoietic reconstitution. One patient died of intracranial infection...
January 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29321823/yin-and-yang-of-mesenchymal-stem-cells-and-aplastic-anemia
#11
REVIEW
Larisa Broglie, David Margolis, Jeffrey A Medin
Acquired aplastic anemia (AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells (HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells (MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis...
December 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29316955/single-molecule-techniques-to-quantify-and-genetically-characterise-persistent-hiv
#12
REVIEW
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
https://www.readbyqxmd.com/read/29315822/chimerism-and-gene-therapy-lessons-learned-from-non-conditioned-murine-bone-marrow-transplantation-models
#13
Katerina Jazbec, Mojca Jež, Boštjan Smrekar, Simona Miceska, Jasmina-Živa Rožman, Urban Švajger, Janja Završnik, Tadej Malovrh, Primož Rožman
OBJECTIVE: Hematopoietic stem and progenitor cells (HSPCs) can be used as a vector for gene therapies. In order to predict the number of HSPCs cells necessary to achieve the target level of chimerism in an autologous setting, syngeneic male bone marrow (BM) cells were transplanted into 35 non-conditioned female BALB/c mice. METHOD: The resulting chimerism was determined at 6-53 weeks by using qPCR, cell subpopulation sorting, and colony-forming units (CFU) analysis...
January 9, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29314206/follicular-lymphoma-2018-update-on-diagnosis-and-management
#14
Arnold Freedman
DISEASE OVERVIEW: Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma (FL) is characterized by diffuse lymphadenopathy, bone marrow involvement, splenomegaly and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. DIAGNOSIS: Diagnosis is based on histology of preferably a biopsy of a lymph node...
February 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29311096/early-detection-and-evolution-of-pre-leukemic-clones-in-therapy-related-myeloid-neoplasms-following-autologous-sct
#15
Gerbrig Berger, Leonie I Kroeze, Theresia N Koorenhof-Scheele, Aniek O de Graaf, Kenichi Yoshida, Hiroo Ueno, Yuichi Shiraishi, Satoru Miyano, Eva van den Berg, Hein Schepers, Bert A van der Reijden, Seishi Ogawa, Edo Vellenga, Joop H Jansen
Therapy-related myeloid neoplasms (tMNs) are severe adverse events that can occur following treatment with autologous hematopoietic stem cell transplantation (ASCT). This study aimed to investigate the development of tMN following ASCT at the molecular level by whole exome sequencing (WES) and targeted deep sequencing (TDS) in sequential (pre-) tMN samples. WES identified a significantly higher number of mutations in tMN as compared to de novo MDS (median 27 vs 12, p=0.001). The mutations found in tMN did not carry a clear ageing-signature, unlike the mutations found in de novo MDS, indicating a different mutational mechanism...
January 8, 2018: Blood
https://www.readbyqxmd.com/read/29305193/ultra-sensitive-droplet-digital-pcr-for-the-assessment-of-microchimerism-in-cellular-therapies
#16
David Kliman, Gloria Castellano-Gonzalez, Barbara Withers, Janine Street, Elizabeth Tegg, Oksana Mirochnik, Joey Lai, Leighton Clancy, David Gottlieb, Emily Blyth
Current techniques to assess chimerism after hematopoietic stem cell transplantation (HSCT) are limited in both sensitivity and precision. These drawbacks are problematic in the context of cellular therapies which frequently result in microchimerism (donor chimerism <1%). We have developed a highly sensitive droplet digital PCR (ddPCR) assay using commercially available regents with good performance throughout the range of clinically relevant chimerism measurements, including microchimerism. We tested the assay using spiked samples of known donor:recipient ratios and in clinical samples from HSCT recipients and patients enrolled on clinical trials of microtransplantation and 3rd party virus specific T cells (VST)...
January 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29300231/long-term-nonhuman-primate-renal-allograft-survival-without-ongoing-immunosuppression-in-recipients-of-delayed-donor-bone-marrow-transplantation
#17
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) following an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine ATG (Atgam) and donor bone marrow transplantation (DBMT). Since these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
January 4, 2018: Transplantation
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#18
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29298288/hierarchically-related-lineage-restricted-fates-of-multipotent-haematopoietic-stem-cells
#19
Joana Carrelha, Yiran Meng, Laura M Kettyle, Tiago C Luis, Ruggiero Norfo, Verónica Alcolea, Francesca Grasso, Adriana Gambardella, Amit Grover, Kari Högstrand, Allegra M Lord, Alejandra Sanjuan-Pla, Petter S Woll, Claus Nerlov, Jacobsen Sten Eirik W
Rare multipotent hematopoietic stem cells (HSCs) in adult bone marrow (BM) with extensive self-renewal potential possess the ability to efficiently replenish all myeloid and lymphoid blood cells1, securing long-term multilineage reconstitution following physiological and clinical challenges, including chemotherapy and hematopoietic transplantations2-4. HSC transplantation remains the only curative treatment for many hematological malignancies, but inefficient blood-lineage replenishment remains a major cause of morbidity and mortality5-6...
January 3, 2018: Nature
https://www.readbyqxmd.com/read/29296868/cord-blood-transplantation-recapitulates-fetal-ontogeny-with-a-distinct-molecular-signature-that-supports-cd4-t-cell-reconstitution
#20
Prashant Hiwarkar, Mike Hubank, Waseem Qasim, Robert Chiesa, Kimberly C Gilmour, Aurore Saudemont, Persis J Amrolia, Paul Veys
Omission of in vivo T-cell depletion promotes rapid, thymic-independent CD4+-biased T-cell recovery after cord blood transplant. This enhanced T-cell reconstitution differs from that seen after stem cell transplant from other stem cell sources, but the mechanism is not known. Here, we demonstrate that the transcription profile of naive CD4+ T cells from cord blood and that of lymphocytes reconstituting after cord blood transplantation is similar to the transcription profile of fetal CD4+ T cells. This profile is distinct to that of naive CD4+ T cells from peripheral blood and that of lymphocytes reconstituting after T-replete bone marrow transplantation...
November 14, 2017: Blood Advances
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