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chronic myeloid

Qingliang Shen, Veer S Bhatt, Inna Krieger, James C Sacchettini, Jae-Hyun Cho
CT-10 regulator of kinase (CRK) proteins play important roles in human cancer metastasis and invasion. Moreover, CRK proteins are the major phosphorylation substrates of ABL kinase and its oncogenic mutant BCR-ABL kinase. The interaction between CRK and BCR-ABL plays important roles in chronic myeloid leukemia. Hence, inhibiting the interaction of CRK with BCR-ABL is an attractive way to attenuate cancer metastasis. Herein, we report the development of a peptide inhibitor, PRM-3, targeting the interaction between CRK-II and ABL kinase...
March 1, 2018: MedChemComm
Huayao Li, Lijuan Liu, Cun Liu, Jing Zhuang, Chao Zhou, Jing Yang, Chundi Gao, Gongxi Liu, Qingliang Lv, Changgang Sun
Qingdai, a traditional Chinese medicine (TCM) used for the treatment of chronic myeloid leukemia (CML) with good efficacy, has been used in China for decades. However, due to the complexity of traditional Chinese medicinal compounds, the pharmacological mechanism of Qingdai needs further research. In this study, we investigated the pharmacological mechanisms of Qingdai in the treatment of CML using network pharmacology approaches. First, components in Qingdai that were selected by pharmacokinetic profiles and biological activity predicted putative targets based on a combination of 2D and 3D similarity measures with known ligands...
August 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Zhihong Hu, Prajwal C Boddu, Sanam Loghavi, Roberto N Miranda, Maitrayee Goswami, L Jeffrey Medeiros, Wayne Tam, Attilio Orazi, Srdan Verstovsek, Sa A Wang
The work-up of patients with hypereosinophilia (HE) is complex. Following the recently revised World Health Organization criteria, we retrospectively reviewed 125 patients who were referred to us to exclude a neoplastic cause of HE (2003-2016). The clinical laboratory work-up confirmed secondary HE in 25 (20%) patients; myeloid/lymphoid neoplasms with rearrangements of PDGFRA (n=9) or PDGFRB (n=2) (9%); HE associated with a well-defined myeloid neoplasm in 8 (6%); and abnormal bone marrow and/or molecular genetic abnormalities consistent with chronic eosinophilic leukemia (CEL), not otherwise specified (NOS) in 21 (17%) patients...
August 13, 2018: American Journal of Hematology
Daniel Xia, Eric D Hsi, Paola Dal Cin, Robert P Hasserjian
No abstract text is available yet for this article.
August 13, 2018: American Journal of Hematology
Maren Kasper, Karoline Walscheid, Björn Laffer, Dirk Bauer, Martin Busch, Lena Wildschütz, Bo Wang, Karin Loser, Thomas Vogl, Rafael S Grajewski, Thomas Langmann, Arnd Heiligenhaus
HLA-B27 is the allele most frequently associated with human anterior uveitis. The majority of HLA-B27-positive [acute anterior uveitis (AAU)] patients develop clinically distinct symptoms with acute symptomatic onset of flare and a recurrent disease course characterized by a massive cellular ocular infiltrate during uveitis relapse. By contrast, uveitis in HLA-B27-negative [idiopathic anterior uveitis (IAU)] patients tends to develop a clinically less fulminant, more chronic, and typically asymptomatic disease course...
2018: Frontiers in Immunology
Neetu Singh, Anil Kumar Tripathi, Dinesh Kumar Sahu, Archana Mishra, Margaret Linan, Bianca Argente, Julia Varkey, Niranjan Parida, Rebecca Chowdhry, Hari Shyam, Nawazish Alam, Shivani Dixit, Pratap Shankar, Abhishek Mishra, Avinash Agarwal, Chris Yoo, Madan Lal Brahma Bhatt, Ravi Kant
Previously, it has been stated that the BCR-ABL fusion-protein is sufficient to induce Chronic Myeloid Leukemia (CML), but additional genomic-changes are required for disease progression. Hence, we profiled control and tyrosine kinase inhibitors (TKI) alone or in combination with other drug-treated CML-samples in different phases, categorized as drug-sensitive and drug-resistant on the basis of BCR-ABL transcripts, the marker of major molecular-response. Molecular-profiling was done using the molecular-inversion probe-based-array, Human Transcriptomics-Array2...
July 13, 2018: Oncotarget
Timothy P Hughes, Pierre Laneuville, Philippe Rousselot, David S Snyder, Delphine Rea, Neil P Shah, David Paar, Elisabetta Abruzzese, Andreas Hochhaus, Jeffrey H Lipton, Jorge E Cortes
Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, both as first-line therapy and after imatinib intolerance or resistance. While generally well tolerated, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors, and outcomes associated with pleural effusion were assessed in two phase 3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11 trials that evaluated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib (including DASISION and 034/Dose-optimization)...
August 9, 2018: Haematologica
Raquel Vinhas, Alexandra Lourenço, Susana Santos, Patrícia Ribeiro, Madalena Silva, Aida Botelho de Sousa, Pedro V Baptista, Alexandra R Fernandes
No abstract text is available yet for this article.
August 9, 2018: Haematologica
Pradnya Chopade, Luke P Akard
Most patients with chronic myeloid leukemia (CML) receiving treatment with BCR-ABL1 tyrosine kinase inhibitors (TKIs) will achieve favorable responses. Moreover, TKI therapy enables patients to experience long-term survival, with survival rates similar to those of individuals without CML. This enhanced survival has resulted from the availability of multiple BCR-ABL1 TKIs with efficacy, not only in frontline treatment, but, importantly, also in second- and third-line treatment. We have reviewed the changes in long-term outcomes in the era of TKI therapy and how these changes have affected treatment practices...
July 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
Melanie Gentil, Patricia Hugues, Christophe Desterke, Gladys Telliam, Ivan Sloma, Lucas E B Souza, Seda Baykal, Jerome Artus, Frank Griscelli, Agnes Guerci, Hyacinthe Johnson-Ansah, Adlen Foudi, Annelise Bennaceur-Griscelli, Ali G Turhan
Aryl Hydrocarbon Receptor (AHR) is an ubiquitous basic helix-loop-helix transcription factor, which is ligand-activated and involved in numerous biological processes including cell division, cell quiescence and inflammation. It has been shown that AHR is involved in normal hematopoietic progenitor proliferation in human cells. In addition, loss of AHR in knockout mice is accompanied by a myeloproliferative syndrome-like disease, suggesting a role of AHR in hematopoietic stem cell (HSC) maintenance. To study the potential role of AHR pathway in CML progenitors and stem cells, we have first evaluated the expression of AHR in UT-7 cell line expressing BCR-ABL...
2018: PloS One
Teresa A Colvin, Pankit Vachhani, Sheila Sait, Vishala Neppalli, Eunice S Wang
A 78-year-old-male with chronic myeloid leukemia (CML) treated for seven years with dasatinib developed an acute promyelocytic leukemia complicated by disseminated intravascular coagulopathy. A promyelocytic blast crisis was diagnosed by demonstrating co-expression of chimeric BCL/ABL and PML/RARα translocations by karyotyping, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction. Promyelocytic blast crisis of CML is a rare event with historically poor outcomes. Treatment of our patient with all- trans -retinoic acid (ATRA) and arsenic trioxide (ATO) resulted in complete morphologic remission...
2018: Leukemia Research Reports
Akanksha Bothale, Kalpana Bothale, Sadhana Mahore, Trupti Dongre
Extramedullary hematopoiesis (EMH) is a compensatory mechanism that occurs when the marrow is unable to maintain sufficient red cell mass. EMH generally occurs in the patients with deficient bone marrow hematopoiesis secondary to either peripheral red cell destruction or marrow replacement. Although EMH is known to occur in agnogenic myeloid metaplasia with myelofibrosis, chronic myelogenous leukemia, thalassemia, and infiltrative disorders, such as lymphomas, it is rare in acute leukemias. EMH is most commonly seen in the liver and spleen as a diffuse lesion...
July 2018: Journal of Cytology
Vipul Sheth, Myriam Labopin, Jonathan Canaani, Liisa Volin, Arne Brecht, Arnold Ganser, Jiri Mayer, Hélène Labussière-Wallet, Jörg Bittenbring, Roni Shouval, Bipin Savani, Mohammad Mohty, Arnon Nagler
FLAMSA followed by sequential reduced intensity conditioning and treosulfan/fludarabine are frequently used conditioning approaches used in centers of the European Society for Blood and Marrow Transplantation (EBMT) for older patients with acute myeloid leukemia (AML). It is currently unknown whether any of these regimens is superior to the others in terms of disease control and toxicity. Using the Acute Leukemia Working Party/EBMT multicenter registry we compared the outcomes of AML patients 45-65 of age transplanted between the years 2007 and 2016...
August 7, 2018: Bone Marrow Transplantation
Moshe Yair Levy, Lisa J McGarry, Hui Huang, Stephanie Lustgarten, Silvia Chiroli, Sergio Iannazzo
OBJECTIVE: Comparing the benefit-risk profiles of ponatinib vs. bosutinib in third-line (3L) treatment of chronic phase chronic myeloid leukemia (CP-CML) is challenging because their pivotal trials lacked comparator arms. To characterize the overall benefit-risk in 3L CP-CML patients treated with bosutinib vs. ponatinib, a matching-adjusted indirect comparison (MAIC) was performed to compare efficacy outcomes and treatment duration after adjusting for trial subjects' baseline characteristics, and tolerability was assessed with an unadjusted comparison of study-drug discontinuation...
August 8, 2018: Current Medical Research and Opinion
J Obst, R Mancuso, E Simon, D Gomez-Nicola
Chronic inflammation is a major driver of neurodegenerative disease and immune regulatory pathways could be potential targets for therapeutic intervention. Recently, Programmed cell death-1 (PD-1) immune checkpoint inhibition has been proposed to mount an IFN-γ-dependent systemic immune response, leading to the recruitment of peripheral myeloid cells to the brain and neuropathological and functional improvements in mice with Alzheimer's disease- like β-amyloid pathology. Here we investigate the impact of PD-1 deficiency on murine prion disease (ME7 strain), a model of chronic neurodegeneration...
August 4, 2018: Brain, Behavior, and Immunity
Hidemitsu Kurosawa, Akihiko Tanizawa, Hideki Muramatsu, Chikako Tono, Akihiro Watanabe, Haruko Shima, Masaki Ito, Yuki Yuza, Kazuko Hamamoto, Noriko Hotta, Masahiko Okada, Akiko Moriya Saito, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Keizo Horibe, Eiichi Ishii, Hiroyuki Shimada
BACKGROUND: The details of the sequential use of imatinib for first-line treatment followed by second-generation tyrosine kinase inhibitors (2G-TKIs) for pediatric chronic myeloid leukemia (CML) are still unknown. This study analyzed clinical responses and adverse effects of the use of 2G-TKIs following imatinib in pediatric chronic phase (CP)-CML. PROCEDURES: The Japanese Pediatric Leukemia/Lymphoma Study Group conducted a retrospective study of patients with newly diagnosed CML from 1996 to 2011...
August 7, 2018: Pediatric Blood & Cancer
Fabien Bastaert, Saadé Kheir, Vinciane Saint-Criq, Bérengère Villeret, Pham My-Chan Dang, Jamel El-Benna, Jean-Claude Sirard, Romé Voulhoux, Jean-Michel Sallenave
Pseudomonas aeruginosa ( P.a ) is a pathogen causing significant morbidity and mortality, in particular, in hospital patients undergoing ventilation and in patients with cystic fibrosis. Among the virulence factors secreted or injected into host cells, the physiopathological relevance of type II secretions system (T2SS) is less studied. Although there is extensive literature on the destructive role of LasB in vitro on secreted innate immune components and on some stromal cell receptors, studies on its direct action on myeloid cells are scant...
2018: Frontiers in Immunology
Gaurav Narula, Maya Prasad, Shalini Jatia, Papagudi G Subramanian, Nikhil Patkar, Prashant Tembhare, Dhanlaxmi Shetty, Nehal Khanna, Siddharth Laskar, Tanuja Shet, Sridhar Epari, Seema Kembhavi, Sneha Shah, Sajid Qureshi, Sumeet Gujral, Shripad D Banavali
INTRODUCTION: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016. MATERIALS AND METHODS: DMG protocols and patient support activities over the study period were documented and audited...
October 2017: Indian Journal of Cancer
Hawk Kim, SooHyun Kim, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Jae-Yong Kwak, Ho-Young Yhim, Sung-Hyun Kim, Young Rok Do, Sukjoong Oh, Sung-Eun Lee, Saengsuree Jootar, Jiu Wei Cui, Dong-Wook Kim
INTRODUCTION: BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed. PATIENTS AND METHODS: A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified...
July 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
Faisal Inayat, Fei Song, Nouman Safdar Ali, Muhammad Haseeb Aslam, Aishatu Aloma, Hilal Hachem, Muhammad Wasif Saif
Patients undergoing cytotoxic or immunosuppressive therapy for cancer have an established predilection for hepatitis B virus reactivation; however, the risk associated with newer molecularly targeted agents has not been well investigated. Imatinib, a small molecule tyrosine kinase inhibitor, induces rapid and sustained clinical benefit by inhibiting a number of signaling pathways, including BCR-ABL and c-KIT. We report the case of a patient who developed hepatitis B virus reactivation while receiving imatinib therapy for gastrointestinal stromal tumor...
August 4, 2018: Journal of Oncology Pharmacy Practice
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