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T cell leukemia

Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin
Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4 -Erucoyl spermidine (designed as N4 -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown...
2018: Epigenetics insights
Chiara Farroni, Emiliano Marasco, Valentina Marcellini, Ezio Giorda, Diletta Valentini, Stefania Petrini, Valentina D'Oria, Marco Pezzullo, Simona Cascioli, Marco Scarsella, Alberto G Ugazio, Giovanni C De Vincentiis, Ola Grimsholm, Rita Carsetti
Children with Down Syndrome (DS) suffer from immune deficiency with a severe reduction in switched memory B cells (MBCs) and poor response to vaccination. Chromosome 21 (HSA21) encodes two microRNAs (miRs), miR-125b, and miR-155, that regulate B-cell responses. We studied B- and T- cell subpopulations in tonsils of DS and age-matched healthy donors (HD) and found that the germinal center (GC) reaction was impaired in DS. GC size, numbers of GC B cells and Follicular Helper T cells (TFH ) expressing BCL6 cells were severely reduced...
2018: Frontiers in Immunology
Kimberly N Smitheman, Tesa M Severson, Satyajit R Rajapurkar, Michael T McCabe, Natalie Karpinich, James Foley, Melissa B Pappalardi, Ashley Hughes, Wendy Halsey, Elizabeth Thomas, Christopher Traini, Kelly E Federowicz, Jenny Laraio, Fredrick Mobegi, Geraldine Ferron-Brady, Rabinder K Prinjha, Christopher L Carpenter, Ryan G Kruger, Lodewyk Wessels, Helai P Mohammad
Lysine specific demethylase 1 (LSD1) is a histone modifying enzyme that suppresses gene expression through demethylation of lysine 4 on histone H3. The anti-tumor activity of GSK2879552 and GSK-LSD1, potent, selective irreversible inactivators of LSD1, has previously been described.1 Inhibition of LSD1 results in a cytostatic growth inhibitory effect in a range of acute myeloid leukemia cell lines. To enhance the therapeutic potential of LSD1 inhibition in this disease setting, a combination of LSD1 inhibition and all-trans retinoic acid was explored...
December 4, 2018: Haematologica
Charles E de Bock, Michelle Down, Kinsha Baidya, Bram Sweron, Andrew W Boyd, Mark Fiers, Gordon F Burns, Timothy J Molloy, Richard B Lock, Jean Soulier, Tom Taghon, Pieter Van Vlierberghe, Jan Cools, Jeff Holst, Rick F Thorne
No abstract text is available yet for this article.
December 4, 2018: Haematologica
Walid Warda, Fabrice Larosa, Mathieu Neto Da Rocha, Rim Trad, Eric Deconinck, Ziad Fajloun, Cyril Faure, Denis Caillot, Marius Moldovan, Severine Valmary-Degano, Sabeha Biichle, Etienne Daguindau, Francine Garnache-Ottou, Sebastien Tabruyn, Olivier Adotévi, Marina Deschamps, Christophe Ferrand
Chronic myeloid leukemia (CML) is a chronic disease resulting in myeloid cell expansion through expression of the BCR-ABL1 fusion transcript. Tyrosine kinase inhibitors (TKI) have significantly increased survival of CML patients, and deep responders may consider stopping the treatment. However, more than 50% of patients relapse and restart TKI, subsequently suffering unknown toxicity. Because CML is a model immune system-sensitive disease, we hypothesize that chimeric antigen receptor (CAR) T cells targeting interleukin-1 receptor-associated protein (IL-1RAP) in quiescent CML stem cells may offer an opportunity for a permanent cure...
December 4, 2018: Cancer Research
Lucas Gutierrez, Miran Jang, Tian Zhang, Mojtaba Akhtari, Houda Alachkar
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy in which the only curative approach is allogeneic stem cell transplant (Allo-HSCT). The recognition and elimination of leukemic clones by donor T-cells contribute significantly to Allo-HSCT success. FLT3-ITD, a common mutation in AML, is associated with poor prognosis. Recently, midostaurin became the first FDA approved FLT3-inhibitor for pre-transplant patients with FLT3-ITD in combination with standard therapy. In addition to their multikinase activity which may affect T-cell signaling, FLT3-inhibitors induce apoptosis of malignant cells which may also enhance antigen presentation to activate T-cells...
December 3, 2018: Scientific Reports
Grace E Benanti, Anne Rain T Brown, Terri Lynn Shigle, Jeffrey J Tarrand, Micah M Bhatti, Patrick M McDaneld, Samuel A Shelburne, Samuel L Aitken
Infections with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL E. coli bacteremia in patients with hematologic malignancy is largely unknown. We conducted a single center, retrospective cohort review of 103 adult inpatients with leukemia and/or hematopoietic stem cell transplant (HCT) recipients with monomicrobial ESBL E. coli bacteremia. No association between increased fourteen-day mortality and empiric treatment with cefepime (8%) or piperacillin-tazobactam (0%) relative to carbapenems (19%) was observed (p = 0...
December 3, 2018: Antimicrobial Agents and Chemotherapy
Chan-Young Ock, Heewon Seo, Dae-Yoon Kim, Byung Joo Min, Yoomi Park, Hyun Sub Cheong, Hyung-Lae Kim, Eun-Young Song, Inho Kim, Sung-Soo Yoon, Ju Han Kim, Youngil Koh
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10-20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c.2982C > T and CDH11 c...
December 3, 2018: Leukemia & Lymphoma
Tania Jain, Mark R Litzow
Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Michael A Pulsipher
Multicenter trials in children and young adults using second-generation CD19-targeted chimeric antigen receptor (CAR) T cells have shown dramatic levels of remission in patients with multiply relapsed/refractory disease (80% to ≥90%). Early results in adult trials have also shown significant responses, and strategies aimed at mitigating toxicities associated with the therapy have improved tolerability. Therefore, if available, CAR T-cell therapy deserves consideration for salvage of children and adults with B-lineage acute lymphoblastic leukemia (B-ALL) who are multiply relapsed, refractory, or relapsed after a previous allogeneic transplantation...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Shira Dinner, Michaela Liedtke
The use of multiagent combination chemotherapy regimens results in cure rates of >90% for children and ∼40% for adults with acute lymphoblastic leukemia (ALL) but is associated with extensive toxicity and disappointingly low efficacy in relapsed patients. ALL blast cells express several surface antigens, including CD20, CD22, and CD19, which represent valuable targets for immunotherapy. Monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell-engaging antibodies targeting these antigens offer novel mechanisms of action...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Su Yeon Yeon, Seung-Hyun Jung, Yun Sol Jo, Eun Ji Choi, Min Sung Kim, Yeun-Jun Chung, Sug Hyung Lee
β2-microglobulin (B2M), a component of major histocompatibility complex class I, plays an important role in host immune reaction to tumor, and inactivation of B2M is known to contribute to resistance to immune checkpoint blockade (ICB) treatment. To further characterize the B2M alterations in tumors, we analyzed B2M hotspot mutations in 2765 benign and malignant tumor tissues by Sanger sequencing and found B2M mutations in 9 (7.5%) microsatellite-unstable (MSU) colorectal cancers (CRCs) and 3 leukemias (0...
November 24, 2018: Pathology, Research and Practice
Mojibade Hassan, Alina Ulezko Antonova, Jian Ming Li, Sakura Hosoba, Manali Rupji, Jeanne Kowalski, Adam J Perricone, David L Jaye, Henry Marsh, Michael Yellin, Steven Devine, Edmund K Waller
Higher numbers of donor plasmacytoid dendritic cells (pDC) increased survival and reduced graft-versus-host disease (GvHD) in human recipients of unrelated donor bone marrow (BM), but not G-CSF peripheral blood grafts. In murine models, we have shown that donor BM pDC increase survival and decrease GvHD compared to G-CSF-mobilized pDC. To increase the content of pDC in BM grafts we studied the effect of FMS-like tyrosine kinase 3 ligand (Flt3L) treatment of murine BM donors on transplant outcomes. Flt3L treatment (300μg/kg/day) resulted in a schedule-dependent increase in the content of pDC in the marrow...
November 29, 2018: Biology of Blood and Marrow Transplantation
María Victoria Nieto Farias, Fernando Nogueira Souza, Pamela Anahí Lendez, Lucía Martínez-Cuesta, Kamila Reis Santos, Alice Maria Melville Paiva Della Libera, María Carolina Ceriani, Guillermina Laura Dolcini
Bovine leukemia virus (BLV) is one of the most important virus in dairy cattle. The infection behavior follows what we call the iceberg phenomenon: 60% of infected animals do not show clinical signs; 30% develop persistent lymphocytosis (PL); and the remaining 10%, die due to lymphosarcoma. BLV transmission depends on infected cell exchange and thus, proviral load is determinant. Understanding the mechanisms by which cattle governs the control of viral dissemination will be desirable for designing effective therapeutic or preventive strategies for BLV...
December 2018: Veterinary Immunology and Immunopathology
B Kipfer, T Daikeler, S Kuchen, M Hallal, N Andina, R Allam, N Bonadies
Myelodysplastic syndromes (MDS) and associated diseases, like chronic myelomonocytic leukemias (CMML), are heterogeneous, clonal disorders affecting the hematopoietic stem cells. They are characterized by dysplasia and a propensity to evolve toward acute myeloid leukemia. Systemic inflammatory and autoimmune manifestations (SIAMs) occur with a prevalence of 10% to 20% in myeloid malignancies, but the underlying pathogenetic mechanisms remain obscure. In this study, we aimed to characterize patient- and disease-based differences in MDS and CMML patients with and without SIAMs and explore the impact of SIAMs on progression and survival...
October 2018: Seminars in Hematology
Sindy Hu, Chien-Wei Chen, Szu-Tah Chen, Ke-Hung Tsui, Tswen-Kei Tang, Hao-Tsai Cheng, Guey-Shyang Hwang, Ju-Wen Yu, Yi-Chieh Li, Paulus S Wang, Shyi-Wu Wang
Berberine is an isoquinoline alkaloid isolated from herb plants, such as Cortex phellodendri (Huangbai) and Rhizoma coptidis (Huanglian). Huanglian and Huangbai have been used as "heat-removing" agents. In addition, berberine has been reported to exert anti-inflammatory effect both in vivo and in vitro, where mitogen-activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) expressions are critically implicated. We herein tested the hypothesis that berberine exerts an anti-inflammatory effect through MAPK and COX-2 signaling pathway in T-cell acute lymphoblastic leukemia (T-ALL)...
November 28, 2018: International Immunopharmacology
Uyen Ngoc Mui, Christopher T Haley, Ramya Vangipuram, Stephen K Tyring
In 1964, the first human oncovirus, Epstein-Barr virus (EBV), was identified in Burkitt lymphoma cells. Since then, six other human oncoviruses have been identified: human papillomavirus (HPV), Merkel cell polyomavirus (MCPyV), hepatitis B and C viruses (HBV and HCV), human T-cell lymphotropic virus-1 (HTLV-1), and human herpesvirus-8 (HHV-8). These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. Additionally, oncoviruses are associated with many benign mucocutaneous diseases...
November 28, 2018: Journal of the American Academy of Dermatology
Fang Bao, Ka Hu, Wei Wan, Lei Tian, Hong-Mei Jing
OBJECTIVE: To investigate the efficacy of CD19-targeted chimeric antigen receptor T-cell (CD19-CAR T) in the treatment of patients with refractory relapsed B cell acute lymphocyte leukemia(B-ALL). METHODS: The efficacy and safety of CD19-CAR T cells in treatment of patients with refractory relapsed B-ALL from January 2015 to July 2017 in the Department of Hematology of Peking University Third Hospital were analyzed retrospectively. RESULTS: A total of 10 patients were included in this analysis, all of which were consistent with the diagnosis of refractory relapsed B-ALL, and the immunophenotype of leukemia cells was CD19 positive...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Navneet S Majhail, Rajshekhar Chakraborty, Gunjan L Shah, Betty K Hamilton, Michael Scordo, Surbhi Sidana
Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric Antigen Receptor-T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, there is a lack of data on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context...
November 27, 2018: Biology of Blood and Marrow Transplantation
Patrick Williams, Sreyashi Basu, Guillermo Garcia-Manero, Christopher S Hourigan, Karolyn A Oetjen, Jorge E Cortes, Farhad Ravandi, Elias J Jabbour, Zainab Al-Hamal, Marina Konopleva, Jing Ning, Lianchun Xiao, Juliana Hidalgo Lopez, Steve M Kornblau, Michael Andreeff, Wilmer Flores, Carlos Bueso-Ramos, Jorge Blando, Pallavi Galera, Katherine R Calvo, Gheath Al-Atrash, James P Allison, Hagop M Kantarjian, Padmanee Sharma, Naval G Daver
BACKGROUND: Phenotypic characterization of immune cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) is lacking. METHODS: T-cell infiltration was quantified on BM biopsies from 13 patients with AML, and flow cytometry was performed on BM aspirates (BMAs) from 107 patients with AML who received treatment at The University of Texas MD Anderson Cancer Center. The authors evaluated the expression of inhibitory receptors (programmed cell death protein 1 [PD1], cytotoxic T-lymphocyte antigen 4 [CTLA4], lymphocyte-activation gene 3 [LAG3], T-cell immunoglobulin and mucin-domain containing-3 [TIM3]) and stimulatory receptors (glucocorticoid-induced tumor necrosis factor receptor-related protein [GITR], OX40, 41BB [a type 2 transmembrane glycoprotein receptor], inducible T-cell costimulatory [ICOS]) on T-cell subsets and the expression of their ligands (41BBL, B7-1, B7-2, ICOSL, PD-L1, PD-L2, and OX40L) on AML blasts...
November 30, 2018: Cancer
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