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https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#1
Lai N Chan, Zhengshan Chen, Daniel Braas, Jae-Woong Lee, Gang Xiao, Huimin Geng, Kadriye Nehir Cosgun, Christian Hurtz, Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Thomas Ernst, Andreas Hochhaus, Steven M Kornblau, Marina Konopleva, Miles A Pufall, Giovanni Cazzaniga, Grace J Liu, Thomas A Milne, H Phillip Koeffler, Theodora S Ross, Isidro Sánchez-García, Arndt Borkhardt, Keith R Yamamoto, Ross A Dickins, Thomas G Graeber, Markus Müschen
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply...
February 13, 2017: Nature
https://www.readbyqxmd.com/read/28191543/the-third-time-chronic-myeloid-leukemia-in-lymphoblastic-crisis-with-abl1-kinase-mutation-induced-by-decitabine-dexamethason-combined-with-nilotinib-and-dasatinib
#2
Suli Wang, Chun Qiao, Yu Zhu, Wenyi Shen, Guangsheng He, Jianyong Li
Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28186983/differentiation-status-of-primary-chronic-myeloid-leukemia-cells-affects-sensitivity-to-bcr-abl1-inhibitors
#3
Paavo O Pietarinen, Christopher A Eide, Pilar Ayuda-Durán, Swapnil Potdar, Heikki Kuusanmäki, Emma I Andersson, John P Mpindi, Tea Pemovska, Mika Kontro, Caroline A Heckman, Olli Kallioniemi, Krister Wennerberg, Henrik Hjorth-Hansen, Brian J Druker, Jorrit M Enserink, Jeffrey W Tyner, Satu Mustjoki, Kimmo Porkka
Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12)...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#4
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28184964/absorption-metabolism-and-excretion-of-14-c-ponatinib-after-a-single-oral-dose-in-humans
#5
Yihua E Ye, Caroline N Woodward, Narayana I Narasimhan
PURPOSE: Ponatinib is a novel tyrosine kinase inhibitor (TKI) specifically designed to inhibit native and mutated BCR-ABL. In the United States, ponatinib has received accelerated approval for adults with T315I-positive chronic myeloid leukemia (CML) or T315I (gatekeeper mutation)-positive, Philadelphia chromosome-positive, acute lymphoblastic leukemia (Ph + ALL), and patients with CML or Ph + ALL for whom no other TKI therapy is indicated. The objective of this phase 1, mass balance study was to evaluate the absorption, metabolism, and excretion of [(14)C]ponatinib in healthy subjects...
February 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28179279/role-of-runx1-in-hematological-malignancies
#6
Raman Sood, Yasuhiko Kamikubo, Paul Liu
RUNX1 is a member of the core binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. RUNX1 is one of the most frequently mutated genes in a variety of hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM). Somatic mutations and chromosomal rearrangements involving RUNX1 are frequently observed in myelodysplastic syndrome (MDS) and leukemias of myeloid and lymphoid lineages, i...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28165340/targeting-the-adenosine-2a-receptor-enhances-chimeric-antigen-receptor-t-cell-efficacy
#7
Paul A Beavis, Melissa A Henderson, Lauren Giuffrida, Jane K Mills, Kevin Sek, Ryan S Cross, Alexander J Davenport, Liza B John, Sherly Mardiana, Clare Y Slaney, Ricky W Johnstone, Joseph A Trapani, John Stagg, Sherene Loi, Lev Kats, David Gyorki, Michael H Kershaw, Phillip K Darcy
Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs)...
February 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28128805/-the-age-and-sex-frequencies-of-patients-with-leukemia-seen-in-two-reference-centers-in-the-metropolitan-area-of-mexico-city
#8
Adrián Santoyo-Sánchez, Christian Omar Ramos-Peñafiel, Azucena Saavedra-González, Lizbeth González-Almanza, Adolfo Martínez-Tovar, Irma Olarte-Carrillo, Juan Collazo-Jaloma
INTRODUCTION: In developing countries, there is commonly a lack of population-based cancer registries or underreporting, thus not recognizing the true dimensions of the problem. AIM: To describe the age and sex frequencies of the major subtypes of leukemias in two hospitals of reference in the metropolitan area of Mexico City. MATERIAL AND METHODS: This is a descriptive and retrospective study, based on medical records of two hematology services during January 2007 to October 2014; all cases diagnosed with leukemia were included...
January 2017: Gaceta Médica de México
https://www.readbyqxmd.com/read/28111465/differential-signaling-networks-of-bcr-abl-p210-and-p190-kinases-in-leukemia-cells-defined-by-functional-proteomics
#9
S Reckel, R Hamelin, S Georgeon, F Armand, Q Jolliet, D Chiappe, M Moniatte, O Hantschel
The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated...
January 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28110394/chimeric-antigen-receptor-car-t-cells-lessons-learned-from-targeting-of-cd19-in-b-cell-malignancies
#10
Kevin A Hay, Cameron J Turtle
Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy...
January 21, 2017: Drugs
https://www.readbyqxmd.com/read/28094079/a-stroke-mimic-methotrexate-induced-neurotoxicity-in-the-emergency-department
#11
Patrick Rogers, Wilbur J Pan, Richard A Drachtman, Christopher Haines
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. The treatment of ALL involves multimodality therapy, and methotrexate (MTX) remains a mainstay of treatment. A complication of MTX therapy includes acute, subacute, and chronic neurotoxocity. Signs and symptoms may range from headaches, dizziness, and mood disorders to seizures and stroke-like symptoms. CASE REPORT: An 18-year-old woman with a history of ALL presented to the emergency department with acute onset of right-sided facial paralysis, right upper extremity flaccid paralysis, and right lower extremity weakness after receiving MTX therapy 3 days earlier...
January 13, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28054750/somatic-med12-nonsense-mutation-escapes-mrna-decay-and-reveals-a-motif-required-for-nuclear-entry
#12
Tuomas Heikkinen, Kati Kämpjärvi, Salla Keskitalo, Pernilla von Nandelstadh, Xiaonan Liu, Ville Rantanen, Esa Pitkänen, Matias Kinnunen, Heikki Kuusanmäki, Mika Kontro, Mikko Turunen, Netta Mäkinen, Jussi Taipale, Caroline Heckman, Kaisa Lehti, Satu Mustjoki, Markku Varjosalo, Pia Vahteristo
MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS)...
March 2017: Human Mutation
https://www.readbyqxmd.com/read/28053192/mature-cd10-and-immature-cd10-neutrophils-present-in-g-csf-treated-donors-display-opposite-effects-on-t-cells
#13
Olivia Marini, Sara Costa, Dalila Bevilacqua, Federica Calzetti, Nicola Tamassia, Cecilia Spina, Donata De Sabata, Elisa Tinazzi, Claudio Lunardi, Maria T Scupoli, Chiara Cavallini, Elisa Zoratti, Ilaria Tinazzi, Antonio Marchetta, Aurora Vassanelli, Maurizio Cantini, Giorgio Gandini, Andrea Ruzzenente, Alfredo Guglielmi, Francesco Missale, William Vermi, Cristina Tecchio, Marco A Cassatella, Patrizia Scapini
The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b(+)-neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28050230/givinostat-a-type-ii-histone-deacetylase-inhibitor-induces-potent-caspase-dependent-apoptosis-in-human-lymphoblastic-leukemia
#14
Ying Li, Kevin Zhao, Chenjiao Yao, Samir Kahwash, Yan Tang, Guojiuan Zhang, Kara Patterson, Qi-En Wang, Weiqiang Zhao
Unlike chronic myeloid leukemia, patients with acute lymphoblastic leukemia (ALL) with Philadelphia chromosome (Ph+) do not respond well to Imatinib or tyrosine kinase inhibitors (TKI). In addition, TKI might induce resistant mutations in kinase domain (KD) of ABL in patients with relapsed diseases. Of the histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic acid (SAHA) has shown to induce potent cytotoxicity on acute myeloid leukemia cell lines but Givinostat effect on acute lymphoblastic leukemia (ALL) has not been reported...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28032244/dasatinib-a-review-in-chronic-myeloid-leukaemia-and-ph-acute-lymphoblastic-leukaemia
#15
Gillian M Keating
Dasatinib (Sprycel(®)) is an orally administered, small molecule inhibitor of multiple tyrosine kinases. In the phase 3 DASISION trial, dasatinib 100 mg once daily resulted in deeper and faster cytogenetic and molecular responses than imatinib 400 mg once daily in patients with newly diagnosed, chronic-phase chronic myeloid leukaemia (CML), although there was no significant between-group difference in progression-free survival (PFS) or overall survival (OS) in the longer term. In the phase 3 CA180-034 trial, a regimen of dasatinib 100 mg once daily provided the most favourable benefit-risk profile in patients with imatinib-resistant or -intolerant chronic-phase CML...
January 2017: Drugs
https://www.readbyqxmd.com/read/28024490/-allogeneic-hematopoietic-stem-cell-transplantation-for-treatment-of-t-cell-lymphoblastic-lymphoma-clinical-observation-of-10-cases
#16
Fang Gong, Heng Chen, Lin-Yan Zhao, Tong Wang, Ri Zhang, De-Pei Wu
OBJECTIVE: To analyze the result of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of patients with T cell Lymphoblastic lymphoma(T-LBL). METHODS: The engraftment, graft versus host disease (GVHD), infection, relapse and survival of 10 T-LBL patients received allo-HSCT was observed. The clinical outcome of allo-HSCT for T-LBL patients was analyzed. RESULTS: The median age of patients was 25 years old, 10 (6 males and 4 females) T-LBL patients received allo-HSCT including 3 from HLA-matched unrelated donors, 3 from HLA-matched sibling donors, 2 from HLA haploidentical sibling donors, and 2 from haploidentical related donors...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28013106/cpx-351-exhibits-potent-and-direct-ex-vivo-cytotoxicity-against-aml-blasts-with-enhanced-efficacy-for-cells-harboring-the-flt3-itd-mutation
#17
Max J Gordon, Paul Tardi, Marc M Loriaux, Stephen E Spurgeon, Elie Traer, Tibor Kovacsovics, Lawrence D Mayer, Jeffrey W Tyner
PURPOSE: Identify AML patients most likely to respond to CPX-351, a nano-scale liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio. METHODS: We examined the ex vivo cytotoxic activity of CPX-351 against leukemic cells isolated from 53 AML patients and an additional 127 samples including acute lymphoblastic leukemia, myelodysplastic syndrome/myeloproliferative neoplasms, or chronic lymphocytic leukemia/lymphoma. We assessed activity with respect to common molecular lesions and used flow cytometry to assess CPX-351 cellular uptake...
December 12, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27983886/graft-versus-host-disease-in-adolescents-and-young-adults-15-24-years-old-after-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-leukemia-in-first-complete-remission
#18
Marguerite Vignon, Annalisa Andreoli, Nathalie Dhédin, Etienne Lengliné, Emeline Masson, Marie Robin, Clémence Granier, Jérôme Larghero, Marie-Hélène Schlageter, Régis Peffault de Latour, Gérard Socié, Nicolas Boissel
PURPOSE: Adolescents and young adults (AYAs) with cancer are a unique group of patients in terms of disease incidence and biology, outcome, and psychosocial needs. This study aims to correlate the risk of graft-versus-host disease (GvHD) and age in a population of children and young adults with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). METHODS: We analyzed the outcome of 153 consecutive children (<15 years), AYAs (15-24 years), and adults (25-35 years) with lymphoblastic or myeloid acute leukemia in first CR who underwent HSCT with matched donors after myeloablative conditioning...
December 16, 2016: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/27981789/comparison-of-abnormal-cell-flagging-of-the-hematology-analyzers-sysmex-xn-and-sysmex-xe-5000-in-oncohematologic-patients
#19
J R Furundarena, M Sainz, A Uranga, L Cuevas, I Lopez, J Zubicaray, A Bizjak, N Robado, M Araiz
INTRODUCTION: Hematology analyzers should optimize flagging while minimizing false-negative results and unnecessary microscopic reviews. METHODS: We compared flagging performance of Sysmex XE-5000 and XN analyzers in oncohematologic patients. Differential counts were performed by Cellavision digital system (100 cells) and a hematologist (another 100 cells). RESULTS: First, we included 292 samples (86 with blasts): 28 acute lymphoblastic leukemia, 88 acute myeloid leukemia, 91 myelodysplastic syndromes, 45 chronic myeloproliferative neoplasms, and 40 chronic myelomonocytic leukemia...
February 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/27977050/the-promise-of-chimeric-antigen-receptor-t-cells-carts-in-leukaemia
#20
REVIEW
Robert J Orlowski, David L Porter, Noelle V Frey
The success of genetically engineered T cells that express chimeric antigen receptors (CARTs) has been a momentous step forward in harnessing the potent cancer fighting abilities of the immune system. The efficacy seen in relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL), not only by inducing remission, but also in maintaining long-term disease control, has been unprecedented. While the foundation for this approach has been firmly set in place, continued development will improve the efficacy, toxicity and applicability to other malignancies of this new class of 'living drugs'...
December 15, 2016: British Journal of Haematology
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