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myeloprolifeative neoplasm

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https://www.readbyqxmd.com/read/29928488/mechanisms-for-mtorc1-activation-and-synergistic-induction-of-apoptosis-by-ruxolitinib-and-bh3-mimetics-or-autophagy-inhibitors-in-jak2-v617f-expressing-leukemic-cells-including-newly-established-pvtl-2
#1
Shinya Ishida, Hiroki Akiyama, Yoshihiro Umezawa, Keigo Okada, Ayako Nogami, Gaku Oshikawa, Toshikage Nagao, Osamu Miura
The activated JAK2-V617F mutant is very frequently found in myeloproliferative neoplasms (MPNs), and its inhibitor ruxolitinib has been in clinical use, albeit with limited efficacies. Here, we examine the signaling mechanisms from JAK2-V617F and responses to ruxolitinib in JAK2-V617F-positive leukemic cell lines, including PVTL-2, newly established from a patient with post-MPN secondary acute myeloid leukemia, and the widely used model cell line HEL. We have found that ruxolitinib downregulated the mTORC1/S6K/4EBP1 pathway at least partly through inhibition of the STAT5/Pim-2 pathway with concomitant downregulation of c-Myc, MCL-1, and BCL-xL as well as induction of autophagy in these cells...
June 1, 2018: Oncotarget
https://www.readbyqxmd.com/read/29926002/utility-of-a-fluorescence-microscopy-imaging-system-for-analyzing-the-dna-ploidy-of-pathological-megakaryocytes-including-5q-syndrome
#2
Takako Nakahara, Shinichiro Suemori, Takayuki Tsujioka, Mikio Kataoka, Hiromi Kataoka, Misako Shibakura, Kaoru Tohyama
To investigate megakaryocyte (MK) DNA ploidy in various hematological diseases, fluorescence microscopy imaging system (FMI) can be used to analyze DNA ploidy with cell morphology at the single-cell level by using specialized image-processing software. Here we compared DNA ploidy obtained by FMI measured with that obtained flow cytometry (FCM). With FMI, we could evaluate the DNA ploidy in long-term preserved bone marrow smear samples after staining. We next analyzed the MK DNA ploidy in 42 bone marrow smear samples including 26 myeloid neoplasm cases, and we compared the DNA ploidy and platelet counts in the patients' peripheral blood; the production of platelets was significantly high compared to DNA ploidy in the myeloproliferative neoplasms group...
June 2018: Acta Medica Okayama
https://www.readbyqxmd.com/read/29907599/aggressive-b-cell-lymphomas-in-patients-with-myelofibrosis-receiving-jak1-2-inhibitor-therapy
#3
Edit Porpaczy, Sabrina Tripolt, Andrea Hoelbl-Kovacic, Bettina Gisslinger, Zsuzsanna Bago-Horvath, Emilio Casanova-Hevia, Emmanuelle Clappier, Thomas Decker, Sabine Fajmann, Daniela A Fux, Georg Greiner, Sinan Gueltekin, Gerwin Heller, Harald Herkner, Gregor Hoermann, Jean-Jacques Kiladjian, Thomas Kolbe, Christoph Kornauth, Maria-Theresa Krauth, Robert Kralovics, Leonhard Muellauer, Mathias Mueller, Michaela Prchal-Murphy, Eva Maria Putz, Emmanuel Raffoux, Ana-Iris Schiefer, Klaus Schmetterer, Christine Schneckenleithner, Ingrid Simonitsch-Klupp, Cathrin Skrabs, Wolfgang R Sperr, Philipp Bernhard Staber, Birgit Strobl, Peter Valent, Ulrich Jaeger, Heinz Gisslinger, Veronika Sexl
Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 MPN patients...
June 14, 2018: Blood
https://www.readbyqxmd.com/read/29904462/langerhans-cell-histiocytosis-of-bone-in-an-adult-a-case-report
#4
Zachary Christopher, Odion Binitie, Evita Henderson-Jackson, Joseph Perno, Rikesh J Makanji
Langerhans cell histiocytosis (LCH) may clinically manifest in a variety of ways due to its ability to involve nearly every organ system. LCH may present as a single bone lesion, skin rash, or as invasive disseminated disease and occurs typically in the pediatric and adolescent population, affecting both males and females. Independent of its clinical presentation and severity, LCH lesions share the common histology of CD1a+ /CD207+ dendritic cells along with an inflammatory infiltrate, and, based upon improved scientific understanding, is now classified as a myeloproliferative neoplasm...
April 2018: Radiology Case Reports
https://www.readbyqxmd.com/read/29899671/hydroxyurea-induced-pneumopathy-in-a-patient-with-myeloproliferative-syndrome
#5
Oriol Plans Galván, Hipólito Pérez Moltó, Ariadna Fabià-Mayans, Blanca Xicoy, José Luis Mate, Pilar Ricart Martí
Hydroxyurea (HU) is a drug frequently used in the treatment of chronic myeloproliferative neoplasms. The most common side effects of this drug are pancytopenia, digestive and skin disorders. Respiratory complications are rare and there are less than 20 cases described, only 5 of which underwent an anatomopathological study. We present the case of a patient with chronic myeloproliferative neoplasm who developed interstitial pneumonitis probably due to HU according to histological study.
2018: Clinical Medicine Insights. Case Reports
https://www.readbyqxmd.com/read/29888803/the-effectiveness-of-exercise-based-rehabilitation-to-patients-with-myeloproliferative-neoplasms-an-explorative-study
#6
Kasper Mønsted Pedersen, Graziella Zangger, Nana Brochmann, Birk Mygind Grønfeldt, Ann-Dorthe Zwisler, Hans Carl Hasselbalch, Lars Hermann Tang
The aim of the study was to determine the impact of an interdisciplinary exercise-based rehabilitation intervention on fatigue and quality of life (QOL) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs). At the Danish Knowledge Centre for Rehabilitation and Palliative Care, a 5-day interdisciplinary exercise-based rehabilitation intervention was carried out on 48 patients with MPN. It was followed by 12 weeks of self-exercising prior to follow-up. Initially and at follow-up, participants filled out validated questionnaires; Brief Fatigue Inventory, Multidimensional Fatigue Inventory, European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire, Myeloproliferative Neoplasm Symptom Assessment Form and Hospital Anxiety and Depression Scale...
June 11, 2018: European Journal of Cancer Care
https://www.readbyqxmd.com/read/29888479/unmasking-and-aggravation-of-polycythemia-vera-by-canagliflozin
#7
L Das, A Bhansali, R Walia
BACKGROUND: Sodium-glucose co-transporter-2 inhibitors are novel antidiabetes drugs that act via inhibition of renal glucose reabsorption. This action causes osmotic diuresis, reduces intravascular volume and is associated with various adverse effects. In the present paper, we describe the first report on the unmasking of underlying polycythemia vera by canagliflozin in a person with Type 2 diabetes mellitus, which was temporally related to the use of the drug. CASE REPORT: A 51-year-old obese man with Type 2 diabetes was prescribed canagliflozin 100 mg for control of his glycaemia...
June 11, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29885533/the-real-world-outcomes-of-treating-polycythemia-vera-physician-adherence-to-treatment-guidelines
#8
Nicholas L Jackson Chornenki, Chatree Chai-Adisaksopha, Darryl P Leong, Deborah M Siegal, Christopher M Hillis
Therapy in Polycythemia Vera (PV), a myeloproliferative neoplasm, focuses on reducing cardiovascular (CV) risk without increasing bleeding or hematological progression. However, the real-world practice of treating PV in North America is understudied. We performed a retrospective cohort study of newly diagnosed PV (JAK2V617F mutation positive) patients in Hamilton, Canada to fill this knowledge gap. Out of 108 patients included, (n = 45, 41.7%) patients did not receive therapy consistent with contemporary treatment guidelines...
June 4, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29884903/mutation-specific-signaling-profiles-and-kinase-inhibitor-sensitivities-of-juvenile-myelomonocytic-leukemia-revealed-by-induced-pluripotent-stem-cells
#9
Sarah K Tasian, Jessica A Casas, David Posocco, Shilpa Gandre-Babbe, Alyssa L Gagne, Ge Liang, Mignon L Loh, Mitchell J Weiss, Deborah L French, Stella T Chou
Juvenile myelomonocytic leukemia (JMML) is an uncommon myeloproliferative neoplasm driven by Ras pathway mutations and hyperactive Ras/MAPK signaling. Outcomes for many children with JMML remain dismal with current standard-of-care cytoreductive chemotherapy and hematopoietic stem cell transplantation. We used patient-derived induced pluripotent stem cells (iPSCs) to characterize the signaling profiles and potential therapeutic vulnerabilities of PTPN11-mutant and CBL-mutant JMML. We assessed whether MEK, JAK, and PI3K/mTOR kinase inhibitors (i) could inhibit myeloproliferation and aberrant signaling in iPSC-derived hematopoietic progenitors with PTPN11 E76K or CBL Y371H mutations...
June 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29878489/chronic-myelomonocytic-leukemia-2018-update-on-diagnosis-risk-stratification-and-management
#10
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (∼15%-20% over 3-5 years). DIAGNOSIS: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼ 30% of patients, while >90% have gene mutations...
June 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29875320/wild-type-kras-expands-and-exhausts-hematopoietic-stem-cells
#11
Joshua P Sasine, Heather A Himburg, Christina M Termini, Martina Roos, Evelyn Tran, Liman Zhao, Jenny Kan, Michelle Li, Yurun Zhang, Stéphanie C de Barros, Dinesh S Rao, Christopher M Counter, John P Chute
Oncogenic Kras expression specifically in hematopoietic stem cells (HSCs) induces a rapidly fatal myeloproliferative neoplasm in mice, suggesting that Kras signaling plays a dominant role in normal hematopoiesis. However, such a conclusion is based on expression of an oncogenic version of Kras. Hence, we sought to determine the effect of simply increasing the amount of endogenous wild-type Kras on HSC fate. To this end, we utilized a codon-optimized version of the murine Kras gene (Krasex3op) that we developed, in which silent mutations in exon 3 render the encoded mRNA more efficiently translated, leading to increased protein expression without disruption to the normal gene architecture...
June 7, 2018: JCI Insight
https://www.readbyqxmd.com/read/29872567/spontaneous-t-cell-responses-against-the-immune-check-point-programmed-death-ligand-1-pd-l1-in-patients-with-chronic-myeloproliferative-neoplasms-correlate-with-disease-stage-and-clinical-response
#12
Morten Orebo Holmström, Caroline Hasselbalch Riley, Vibe Skov, Inge Marie Svane, Hans Carl Hasselbalch, Mads Hald Andersen
The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29868160/a-case-of-massive-splenomegaly-due-to-chronic-myeloproliferative-neoplasm
#13
Zachary G Jacobs, Bongani Kaimila, Peter M Wasswa, Thuy Bui
No abstract text is available yet for this article.
March 2018: Malawi Medical Journal: the Journal of Medical Association of Malawi
https://www.readbyqxmd.com/read/29867515/npv-bsk805-an-antineoplastic-jak2-inhibitor-effective-in-myeloproliferative-disorders-causes-adiposity-in-mice-by-interfering-with-the-action-of-leptin
#14
Magalie Haissaguerre, Amandine Ferriere, Samantha Clark, Omar Guzman-Quevedo, Antoine Tabarin, Daniela Cota
The pathophysiology of body weight gain that is observed in patients suffering from myeloproliferative neoplasms treated with inhibitors of the janus kinase (Jak) 1 and 2 pathway remains unknown. Here we hypothesized that this class of drugs interferes with the metabolic actions of leptin, as this hormone requires functional Jak2 signaling. To test this, C57BL/6J chow-fed mice received either chronic intraperitoneal (ip) or repeated intracerebroventricular (icv) administration of the selective Jak2 inhibitor NVP-BSK805, which was proven efficacious in treating polycythemia in rodents...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29866231/lenalidomide-induced-toxic-epidermal-necrolysis-and-del-5q-co-occurrence-of-rarities
#15
Qamar Un Nisa Chaudhry, Raheel Iftikhar, Tariq Mehmood Satti, Syed Kamran Mahmood, Mehreen Ali Khan, Nighat Shahbaz
Primary myelofibrosis (PMF) is a clonal, BCR-ABL1 negative myeloproliferative neoplasm characterised by splenomegaly, leukoerythroblastic peripheral blood picture and bone marrow fibrosis. Different cytogentic abnormalities are documented in PMF which have impact on clinical outcome and overall survival. Del 5q31 is documented in only 0.8% of PMF patients and is associated with poor outcome and increased risk of progression to acute leukemia. Anemia with del 5q responds frequently to lenalidomide treatment...
June 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29851963/serum-of-myeloproliferative-neoplasms-stimulates-hematopoietic-stem-and-progenitor-cells
#16
Richard K Lubberich, Thomas Walenda, Tamme W Goecke, Klaus Strathmann, Susanne Isfort, Tim H Brümmendorf, Steffen Koschmieder, Wolfgang Wagner
BACKGROUND: Myeloproliferative neoplasms (MPN)-such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF)-are typically diseases of the elderly caused by acquired somatic mutations. However, it is largely unknown how the malignant clone interferes with normal hematopoiesis. In this study, we analyzed if serum of MPN patients comprises soluble factors that impact on hematopoietic stem and progenitor cells (HPCs). METHODS: CD34+ HPCs were cultured in medium supplemented with serum samples of PV, ET, or MF patients, or healthy controls...
2018: PloS One
https://www.readbyqxmd.com/read/29847855/implications-of-mutation-profiling-in-myeloid-malignancies-part-2-myeloproliferative-neoplasms-and-other-myeloid-malignancies
#17
REVIEW
Kelsey Sokol, Douglas Tremblay, Sheena Bhalla, Raajit Rampal, John O Mascarenhas
Myeloid malignancies arise from the acquisition of somatic mutations among various genes implicated in essential functioning of hematopoietic stem cells and progenitor cells. In this second part of our two-part review, we discuss the use of mutation profiling in the diagnosis, prognosis, and treatment of patients with myeloproliferative neoplasms and other myeloid diseases. We also discuss the entity known as clonal hematopoiesis of indeterminate potential, awareness of which is a result of the increasing availability and improved quality of mutation profiling...
May 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/29845291/concomitant-presence-of-jak2v617f-mutation-and-bcr%C3%A2-abl-translocation-in-two-patients-a-new-entity-or-a-variant-of-myeloproliferative-neoplasms-case-report
#18
Filipa Mousinho, Ana P Azevedo, Tatiana Mendes, Paula Sousa E Santos, Rita Cerqueira, Sónia Matos, Sónia Santos, Sância Ramos, João Faro Viana, Fernando Lima
Myeloproliferative neoplasms (MPNs) are classically divided into BCR RhoGEF and GTPase activating protein (BCR)-ABL proto‑oncogene 1 non‑receptor tyrosine kinase (ABL) positive chronic myeloid leukemia (CML) and BCR‑ABL negative MPNs, including essential thrombocythemia (ET). One of the major diagnostic criteria for ET is the absence of the philadelphia chromosome, thus when present it is almost indicative of CML. ET and CML are considered to be mutually exclusive; however, there are rare situations in which patients with ET present positive BCR‑ABL without the features of CML...
May 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29843123/the-critical-role-of-pten-pi3k-akt-signaling-pathway-in-shikonin-induced-apoptosis-and-proliferation-inhibition-of-chronic-myeloid-leukemia
#19
Yu Chen, Tongtong Wang, Jing Du, Yanchun Li, Xin Wang, Yi Zhou, XingXing Yu, Weimin Fan, Qiaojuan Zhu, Xiangmin Tong, Ying Wang
BACKGROUND/AIMS: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line...
May 24, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29842959/effects-of-jak2-v556f-mutation-on-the-jak2-s-activity-structural-stability-and-the-transformation-of-ba-f3-cells
#20
Qing-Yun Wu, Meng-Meng Ma, Yu-Xue Tong, Yuan-Yuan Zhu, Yang Liu, Jiang Cao, Ping Zhou, Zhen-Yu Li, Ling-Yu Zeng, Xiao-Yun Wang, Feng Li, Kai-Lin Xu
Although roles of somatic JAK2 mutations in clonally myeloproliferative neoplasms (MPNs) are well established, roles of germline JAK2 mutations in the pathogenesis of MPNs remain unclear. Recently, a novel activating, germline JAK2 F556V mutation was identified and involved in the pathogenesis of MPNs, but, its pathogenesis mechanism was still unknown. In this study, homology models of JAK2 demonstrated that F556 located between two threonine residues which interacted with ATP phosphate groups by hydrogen bonds, Thr555 with the γ-phosphate and Thr557 with the β-phosphate in the active site of JAK2's JH2 domain...
May 26, 2018: International Journal of Biological Macromolecules
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