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https://www.readbyqxmd.com/read/29217783/somatic-stat3-mutations-in-the-felty-syndrome-an-implication-for-a-common-pathogenesis-with-large-granular-lymphocyte-leukemia
#1
Paula Savola, Oscar Brück, Thomas Olson, Tiina Kelkka, Markku J Kauppi, Panu E Kovanen, Soili Kytölä, Tuulikki Sokka-Isler, Thomas P Loughran, Marjatta Leirisalo-Repo, Satu Mustjoki
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. We now aimed to study whether these mutations can also be detected in Felty syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29216917/unexpected-profile-of-sphingolipid-contents-in-blood-and-bone-marrow-plasma-collected-from-patients-diagnosed-with-acute-myeloid-leukemia
#2
Marzena Wątek, Bonita Durnaś, Tomasz Wollny, Marcin Pasiarski, Stanisław Góźdź, Michał Marzec, Anna Chabowska, Przemysław Wolak, Małgorzata Żendzian-Piotrowska, Robert Bucki
BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main factor of leukemic cells drug resistance. METHODS: To assess the presence of potential abnormalities that might promote dysfunction of leukemic cells growth, HPLC system was used to determine sphingosine (SFO), sphinganine (SFA), sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49) and compare to values of control (healthily) group (n = 51)...
December 8, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29209044/biological-and-prognostic-impact-of-apobec-induced-mutations-in-the-spectrum-of-plasma-cell-dyscrasias-and-multiple-myeloma-cell-lines
#3
F Maura, M Petljak, M Lionetti, I Cifola, W Liang, E Pinatel, L Alexandrov, A Fullam, I Martincorena, K J Dawson, N Angelopoulos, M K Samur, R Szalat, J Zamora, P Tarpey, H Davies, P Corradini, K Anderson, S Minvielle, A Neri, H Avet-Loiseau, J J Keats, P J Campbell, N Munshi, N Bolli
Leukemia accepted article preview online, 06 December 2017. doi:10.1038/leu.2017.345.
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29202792/the-cc-chemokine-ligand-ccl-1-upregulated-by-the-viral-transactivator-tax-can-be-downregulated-by-minocycline-possible-implications-for-long-term-treatment-of-htlv-1-associated-myelopathy-tropical-spastic-paraparesis
#4
Mineki Saito, Hiroe Sejima, Tadasuke Naito, Hiroshi Ushirogawa, Toshio Matsuzaki, Eiji Matsuura, Yuetsu Tanaka, Tatsufumi Nakamura, Hiroshi Takashima
BACKGROUND: Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/ macrophages and T-lymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
December 4, 2017: Virology Journal
https://www.readbyqxmd.com/read/29202702/c-reactive-protein-crp-but-not-the-related-pentraxins-serum-amyloid-p-and-ptx3-inhibits-the-proliferation-and-induces-apoptosis-of-the-leukemia-cell-line-mono-mac-6
#5
Wensheng Chen, Darrell Pilling, Richard H Gomer
BACKGROUND: Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages. C-reactive protein (CRP) is a plasma protein whose levels can rise to 1000 μg/ml from the normal <3 μg/ ml during inflammation. RESULTS: We find that CRP inhibits proliferation of the human myeloid leukemia cell line Mono Mac 6 with an IC50 of 75 μg/ ml by inducing apoptosis of these cells. The related proteins serum amyloid P (SAP) and pentraxin 3 (PTX3) do not inhibit Mono Mac 6 proliferation...
December 4, 2017: BMC Immunology
https://www.readbyqxmd.com/read/29182633/extensive-virologic-and-immunologic-characterization-in-an-hiv-infected-individual-following-allogeneic-stem-cell-transplant-and-analytic-cessation-of-antiretroviral-therapy-a-case-study
#6
Nathan W Cummins, Stacey Rizza, Mark R Litzow, Stephane Hua, Guinevere Q Lee, Kevin Einkauf, Tae-Wook Chun, Frank Rhame, Jason V Baker, Michael P Busch, Nicolas Chomont, Patrick G Dean, Rémi Fromentin, Ashley T Haase, Dylan Hampton, Sheila M Keating, Steven M Lada, Tzong-Hae Lee, Sekar Natesampillai, Douglas D Richman, Timothy W Schacker, Stephen Wietgrefe, Xu G Yu, Joseph D Yao, John Zeuli, Mathias Lichterfeld, Andrew D Badley
BACKGROUND: Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. METHODS AND FINDINGS: We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29179486/functional-expression-of-tim-3-on-blasts-and-clinical-impact-of-its-ligand-galectin-9-in-myelodysplastic-syndromes
#7
Toshio Asayama, Hideto Tamura, Mariko Ishibashi, Yasuko Kuribayashi-Hamada, Asaka Onodera-Kondo, Namiko Okuyama, Akiko Yamada, Masumi Shimizu, Keiichi Moriya, Hidemi Takahashi, Koiti Inokuchi
T-cell immunoglobulin mucin-3 (Tim-3), an inhibitory immune checkpoint receptor, is highly expressed on acute myeloid leukemia cells and its ligand galectin-9 is reported to drive leukemic progression by binding with Tim-3. However, it remains unclear whether the Tim-3-galectin-9 pathway is associated with the pathophysiology of myelodysplastic syndromes (MDS). Thus, we investigated the expression and function of Tim-3 and the clinical impact of its ligand galectin-9 in MDS. Tim-3 expression levels on MDS blasts by CD45/side-scatter or CD34/CD45 gating were increased as MDS progressed to the advanced stage...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29179437/high-glucose-promotes-vascular-smooth-muscle-cell-proliferation-by-upregulating-proto-oncogene-serine-threonine-protein-kinase-pim-1-expression
#8
Keke Wang, Xiaojiang Deng, Zhihua Shen, Yanan Jia, Ranran Ding, Rujia Li, Xiaomin Liao, Sisi Wang, Yanping Ha, Yueqiong Kong, Yuyou Wu, Junli Guo, Wei Jie
Serine/threonine kinase proviral integration site for Moloney murine leukemia virus 1 (Pim-1) plays an essential role in arterial wall cell proliferation and associated vascular diseases, including pulmonary arterial hypertension and aortic wall neointima formation. Here we tested a role of Pim-1 in high-glucose (HG)-mediated vascular smooth muscle cell (VSMC) proliferation. Pim-1 and proliferating cell nuclear antigen (PCNA) expression levels in arterial samples from streptozotocin-induced hyperglycemia rats were increased, compared with their weak expression in normoglycemic groups...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29178667/comprehensive-review-of-post-organ-transplant-hematologic-cancers
#9
Vikas R Dharnidharka
A higher risk for a variety of cancers is among the major complications of post-transplant immunosuppression. In this part of a continuing series on cancers post-transplant, this review focuses on the hematologic cancers after solid organ transplant. Post-transplant lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non-Hodgkin lymphomas. The oncogenic Epstein-Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms...
November 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29174474/iron-overload-in-hematological-disorders
#10
Eitan Fibach, Eliezer A Rachmilewitz
While most common symptom of impairment of iron homeostasis is iron deficiency anemia, some hematological disorders are associated with iron overload (IO). These disorders are related mainly to chronic severe hemolytic anemia, where red blood cells (RBC) or their precursors are destroyed prematurely (hemolyzed), leading to anemia that cannot be compensated by increased production of new RBC. In such cases, IO is mainly due to repeated RBC transfusions and/or increased uptake of iron in the gastrointestinal tract...
November 22, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29171939/initial-flow-cytometric-evaluation-of-the-clearllab-lymphoid-screen
#11
B D Hedley, G Cheng, J Luider, W Kern, G Lozanski, I Chin-Yee, L E Lowes, M Keeney, D Careaga, R Magari, L Tejidor
INTRODUCTION: Flow cytometric immunophenotyping (FCI) is an integral part in the diagnosis and classification of hematologic malignancies. FCI results also influence therapeutic decisions and disease prognosis. ClearLLab LS is a 12-antibody 10-color cocktail provided in dry format designed as a screen for patients suspected of having hematolymphoid disease. METHODS: A blinded comparison between ClearLLab LS, (CD8-FITC,Kappa-FITC,CD4-PE,Lambda-PE,CD19-ECD,CD56-PE-Cy5...
November 24, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29168399/vacuolar-atpase-as-a-possible-therapeutic-target-in-human-acute-myeloid-leukemia
#12
Elise Aasebø, Sushma Bartaula-Brevik, Maria Hernandez-Valladares, Øystein Bruserud
V-ATPase is a proton pump expressed both in the membrane of intracellular organelles (e.g. endosomes, lysosomes, Golgi structures) and the plasma membrane. It is an important regulator of organellar functions, intracellular molecular trafficking, intercellular communication and intracellular signaling. It is therefore considered as a possible therapeutic target in the treatment of human malignancies. Areas covered: Relevant publications were identified through literature searches in the PubMed database. We searched for original articles and reviews describing the possible importance of V-ATPase for leukemogenesis and chemosensitivity in human myeloid cells, especially acute myeloid leukemia (AML) cells...
November 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29163182/the-natural-antiangiogenic-compound-ad0157-induces-caspase-dependent-apoptosis-in-human-myeloid-leukemia-cells
#13
Melissa García-Caballero, Beatríz Martínez-Poveda, Miguel A Medina, Ana R Quesada
Evasion of apoptosis is a hallmark of cancer especially relevant in the development and the appearance of leukemia drug resistance mechanisms. The development of new drugs that could trigger apoptosis in aggressive hematological malignancies, such as AML and CML, may be considered a promising antileukemic strategy. AD0157, a natural marine pyrrolidinedione, has already been described as a compound that inhibits angiogenesis by induction of apoptosis in endothelial cells. The crucial role played by defects in the apoptosis pathways in the pathogenesis, progression and response to conventional therapies of several forms of leukemia, moved us to analyze the effect of this compound on the growth and death of leukemia cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29158376/leukemia-specific-delivery-of-mutant-notch1-targeted-therapy
#14
Giovanni Roti, Jun Qi, Samuel Kitara, Marta Sanchez-Martin, Amy Saur Conway, Anthony C Varca, Angela Su, Lei Wu, Andrew L Kung, Adolfo A Ferrando, James E Bradner, Kimberly Stegmaier
On-target drug delivery remains a challenge in cancer precision medicine; it is difficult to deliver a targeted therapy to cancer cells without incurring toxicity to normal tissues. The SERCA (sarco-endoplasmic reticulum Ca2+ ATPase) inhibitor thapsigargin inhibits mutant NOTCH1 receptors compared with wild type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic in humans. Leveraging the addiction of ALL to folic acid, we conjugated folate to an alcohol derivative of thapsigargin via a cleavable ester linkage...
November 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29153308/leukapheresis-do-not-improve-early-death-rates-in-acute-myeloid-leukemia-patients-with-hyperleukocytosis
#15
Umit Yavuz Malkan, Osman Ilhami Ozcebe
Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm(3) in peripheral blood. It has been already shown in the literature that leukapheresis, a conventional technique to decrease the serum WBC level, is ineffective for long-term survival in cases of hyperleukocytotic acute myeloid leukemia (AML) with leukostasis. However, the effect of leukapheresis on early mortality is still unclear. In this study, we aimed to evaluate the effect of leukapheresis on early mortality of patients with AML who have HL...
November 8, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29149251/parental-age-and-risk-of-lymphoid-neoplasms
#16
Gunnar Larfors, Ingrid Glimelius, Sandra Eloranta, Karin E Smedby
High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29148541/integrated-genomic-analysis-identifies-deregulated-jak-stat-myc-biosynthesis-axis-in-aggressive-nk-cell-leukemia
#17
Liang Huang, Dan Liu, Na Wang, Shaoping Ling, Yuting Tang, Jun Wu, Lingtong Hao, Hui Luo, Xuelian Hu, Lingshuang Sheng, Lijun Zhu, Di Wang, Yi Luo, Zhen Shang, Min Xiao, Xia Mao, Kuangguo Zhou, Lihua Cao, Lili Dong, Xinchang Zheng, Pinpin Sui, Jianlin He, Shanlan Mo, Jin Yan, Qilin Ao, Lugui Qiu, Hongsheng Zhou, Qifa Liu, Hongyu Zhang, Jianyong Li, Jie Jin, Li Fu, Weili Zhao, Jieping Chen, Xin Du, Guoliang Qing, Hudan Liu, Xin Liu, Gang Huang, Ding Ma, Jianfeng Zhou, Qian-Fei Wang
Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm that is more prevalent among people from Asia and Central and South America. Patients usually die within days to months, even after receiving prompt therapeutic management. Here we performed the first comprehensive study of ANKL by integrating whole genome, transcriptome and targeted sequencing, cytokine array as well as functional assays. Mutations in the JAK-STAT pathway were identified in 48% (14/29) of ANKL patients, while the extracellular STAT3 stimulator IL10 was elevated by an average of 56-fold (P < 0...
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29146910/an-unexpected-protein-interaction-promotes-drug-resistance-in-leukemia
#18
Aaron Pitre, Yubin Ge, Wenwei Lin, Yao Wang, Yu Fukuda, Jamshid Temirov, Aaron H Phillips, Jennifer L Peters, Yiping Fan, Jing Ma, Amanda Nourse, Chandrima Sinha, Hai Lin, Richard Kriwacki, James R Downing, Tanja A Gruber, Victoria E Centonze, Anjaparavanda P Naren, Taosheng Chen, John D Schuetz
The overall survival of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related therapeutic targets remains a major goal for this disease. Here we show that expression of MPP1, a PDZ-domain-containing protein, highly correlated with ABCC4 in AML, is associated with worse overall survival in AML. Murine hematopoietic progenitor cells overexpressing MPP1 acquired the ability to serially replate in methylcellulose culture, a property crucially dependent upon ABCC4. The highly conserved PDZ-binding motif of ABCC4 is required for ABCC4 and MPP1 to form a protein complex, which increased ABCC4 membrane localization and retention, to enhance drug resistance...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29140406/smad3-stat3-crosstalk-in-pathophysiological-contexts
#19
Yuka Itoh, Masao Saitoh, Keiji Miyazawa
Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others...
November 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29136959/alterations-of-biomechanics-in-cancer-and-normal-cells-induced-by-doxorubicin
#20
Kaja Fraczkowska, Marcin Bacia, Magda Przybyło, Dominik Drabik, Aleksandra Kaczorowska, Justyna Rybka, Ewa Stefanko, Slawomir Drobczynski, Jan Masajada, Halina Podbielska, Tomasz Wrobel, Marta Kopaczynska
Mechanical properties of biological structures play an important role in regulating cellular activities and are critical for understanding metabolic processes in cancerous cells and the effects of drugs. For some cancers, such as acute myeloid leukaemia, chemotherapy is one of preferential methods. However, due to the lack of selectivity to cancer cells, cytostatic agents cause toxicity to normal tissues. Here, we study the effect of doxorubicin (DOX) on the mechanical properties of DNA molecules, leukemic blast cells and erythrocytes, using optical tweezers...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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