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https://www.readbyqxmd.com/read/30516071/microrna-221-sensitizes-chronic-myeloid-leukemia-cells-to-imatinib-by-targeting-stat5
#1
Xiaoxiao Jiang, Yanhong Cheng, Chaojie Hu, Aimei Zhang, Yingli Ren, Xiucai Xu
MicroRNAs (miRNAs) are involved in various processes from the development to drug resistance of tumors, including chronic myeloid leukemia (CML). In this study, we examined the STAT5-related miRNA-expression profile in CML cell lines (K562 and imatinib-resistant K562/G) by quantitative real-time reverse-transcriptase polymerase chain reactions. MiR-221 expression was markedly decreased in K562/G cells and peripheral blood mononuclear cells from patients with treatment failure, when compared to imatinib-sensitive CML cells and patients with optimal responses respectively...
December 5, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/30514803/imatinib-dose-reduction-in-major-molecular-response-of-chronic-myeloid-leukemia-results-from-the-german-chronic-myeloid-leukemia-study-iv
#2
Christian Michel, Andreas Burchert, Andreas Hochhaus, Susanne Saussele, Andreas Neubauer, Michael Lauseker, Stefan W Krause, Hans-Jochem Kolb, Dieter Kurt Hossfeld, Christoph Nerl, Gabriela M Baerlocher, Dominik Heim, Tim H Brümmendorf, Alice Fabarius, Claudia Haferlach, Brigitte Schlegelberger, Leopold Balleisen, Maria-Elisabeth Goebeler, Mathias Hänel, Anthony Ho, Jolanta Dengler, Christiane Falge, Robert Möhle, Stephan Kremers, Michael Kneba, Frank Stegelmann, Claus-Henning Köhne, Hans-Walter Lindemann, Cornelius F Waller, Karsten Spiekermann, Wolfgang E Berdel, Lothar Müller, Matthias Edinger, Jiri Mayer, Dietrich W Beelen, Martin Bentz, Hartmut Link, Bernd Hertenstein, Roland Fuchs, Martin Wernli, Frank Schlegel, Rudolf Schlag, Maike de Wit, Lorenz Trümper, Holger Hebart, Markus Hahn, Jörg Thomalla, Christof Scheid, Philippe Schafhausen, Walter Verbeek, Michael J Eckart, Winfried Gassmann, Michael Schenk, Peter Brossart, Thomas Wündisch, Thomas Geer, Stephan Bildat, Erhardt Schäfer, Joerg Hasford, Rüdiger Hehlmann, Markus Pfirrmann
Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800mg (high-dose) imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800mg to 400mg daily in the Chronic Myeloid Leukemia-Study IV...
December 4, 2018: Haematologica
https://www.readbyqxmd.com/read/30514753/cml-hematopoietic-stem-cells-expressing-il-1rap-can-be-targeted-by-chimeric-antigen-receptor-car-engineered-t-cells
#3
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
https://www.readbyqxmd.com/read/30511400/ikzf1-deletion-and-co-occurrence-with-other-aberrations-in-a-child-with-chronic-myeloid-leukemia-progressing-to-acute-lymphoblastic-leukemia
#4
Claudete Esteves Klumb, Thayana da Conceição Barbosa, Gabriela Nestal de Moraes, Marcia Trindade Schramm, Mariana Emerenciano, Raquel Ciuvalschi Maia
Chronic myeloid leukemia (CML) is a rare disease in children. Different from that in adults, childhood CML involves transformative events occurring over a short time period. CML transformation to lymphoid blast phase (BP) is associated with copy number abnormalities, characteristic of BCR-ABL1 positive acute lymphoblastic leukemia, but not of CML in the chronic phase. Here, we present an unusual case of CML progressing to BP in a 1.6-year-old child, harboring IKZF1, PAX5, CDKN2A, and ETV6 deletions at diagnosis...
December 4, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/30511314/salvage-and-bridging-to-allogeneic-hematopoietic-cell-transplantation-with-ponatinib-in-patients-with-relapsed-or-refractory-philadelphia-chromosome-positive-leukemia
#5
Takayoshi Tachibana, Satoshi Koyama, Taiki Andou, Yasufumi Ishiyama, Masatsugu Tanaka, Hideaki Nakajima, Heiwa Kanamori
A single-center retrospective study was performed with consecutive patients who received salvage therapy using ponatinib for the aim of allogeneic hematopoietic cell transplantation (HCT) for relapsed or refractory Ph-leukemia between January 2017 and July 2018. A total of ten patients-seven with Ph-acute lymphoblastic leukemia (ALL) and three with chronic phase (CP)/accelerated phase chronic myeloid leukemia (CML)-were eligible. Eight patients had a history of a single tyrosine kinase inhibitor (TKI) use prior to ponatinib...
December 3, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/30509616/potential-leukemic-cells-engraftment-after-hematopoietic-stem-cell-transplantation-from-unrelated-donors-with-undiagnosed-chronic-leukemia
#6
M P Kawa, B Baumert, Z Litwińska, M Gniot, E Pius-Sadowska, D Rogińska, K Lewandowski, B Zdziarska, B Machaliński
BACKGROUND: Donor-related neoplasms are a potential complication of treatment strategies involving stem cell transplantation. Although mechanisms for detection of short-term complications after these procedures are well developed, complications with delayed onset, notably transmission of chronic diseases such as chronic myeloid leukemia (CML), have been difficult to assess. Consequently, we studied the potential of human CML cells to engraft hematopoietic tissues after intravenous implantation in mice...
April 18, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/30508560/eomes-expressing-t-helper-cells-as-potential-target-of-therapy-in-chronic-neuroinflammation
#7
REVIEW
Shinji Oki
Reserch progresses in understanding the pathogenicity of multiple sclerosis (MS) in the last couple of decade has enabled us to develop new drug entities available in the clinic. However, we still have not succeeded in preventing conversion from relapsing-remitting MS (RR-MS) to secondary progressive MS (SP-MS) and curing this intractable form of MS. Furthermore, diagnosis is usually retrospective and subjective, relying on gradual worsening of neurological signs/symptoms. This is obviously due to the lack of understanding for the pathogenicity driving disease progression in MS and of reliable biomarkers reflecting the progressive or stationary disease status...
November 30, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/30504932/feasibility-of-treatment-discontinuation-in-chronic-myeloid-leukemia-in-clinical-practice-results-from-a-nationwide-series-of-236-patients
#8
Juan Carlos Hernández-Boluda, Arturo Pereira, Irene Pastor-Galán, Alberto Alvarez-Larrán, Alisa Savchuk, José Manuel Puerta, José María Sánchez-Pina, Rosa Collado, Alvaro Díaz-González, Anna Angona, Miguel Sagüés, Valentín García-Gutiérrez, Concepción Boqué, Santiago Osorio, Rolando Vallansot, Luis Palomera, Arantxa Mendizábal, Luis Felipe Casado, Manuel Pérez-Encinas, Raúl Pérez-López, Francisca Ferrer-Marín, Fermín Sánchez-Guijo, Carmen García, Natalia de Las Heras, José Luis López-Lorenzo, Francisco Cervantes, Juan Luis Steegmann
Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Median follow-up from treatment discontinuation was 21.5 months and 5 patients died from CML-unrelated causes. TKI therapy was reinitiated due to MMR loss (n = 52), increase ≥ 1 log in BCR-ABL transcript level without losing MMR (n = 12), patient preference (n = 2), and withdrawal syndrome (n = 1)...
December 2, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/30504658/-met-erk-and-met-jnk-pathway-activation-is-involved-in-bcr-abl-inhibitor-resistance-in-chronic-myeloid-leukemia
#9
Masanobu Tsubaki
Resistance to the breakpoint cluster region-abelson (BCR-ABL) tyrosine kinase inhibitor (TKI), imatinib, poses a major problem in the treatment of chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, the basis of this BCR-ABL1-independent resistance in the absence of such mutation remains to be elucidated. The aim of the present study is to identify the mechanism of imatinib resistance in CML. To gain insight into BCR-ABL1-independent imatinib resistance mechanisms, we performed an array-based comparative genomic hybridization...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/30504307/we-do-still-transplant-cml-don-t-we
#10
REVIEW
Charles F Craddock
The remarkable clinical activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has transformed patient outcome. Consequently, allogeneic stem cell transplantation (allo-SCT) is no longer the only treatment modality with the ability to deliver long-term survival. In contrast to the central position it held in the treatment algorithm 20 years ago, allografting is now largely reserved for patients with either chronic-phase disease resistant to TKI therapy or advanced-phase disease. Over the same period, progress in transplant technology, principally the introduction of reduced intensity conditioning regimens coupled with increased donor availability, has extended transplant options in patients with CML whose outcome can be predicted to be poor if they are treated with TKIs alone...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/30504306/molecular-monitoring-in-cml-how-deep-how-often-how-should-it-influence-therapy
#11
REVIEW
Naranie Shanmuganathan, Timothy P Hughes
With the advent of tyrosine kinase inhibitors (TKIs), the goals of therapy in chronic myeloid leukemia (CML) are steadily shifting. Long-term disease control on TKI therapy has been the goal and expectation for most patients. More recently, treatment-free remission (TFR) has entered mainstream practice and is increasingly being adopted as the main goal of therapy. This therapeutic shift not only influences TKI selection but also, has necessitated the refinement and dissemination of highly sensitive and accurate molecular monitoring techniques...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/30504305/the-argument-for-using-imatinib-in-cml
#12
REVIEW
Simone Claudiani, Jane F Apperley
June 2018 was the 20th anniversary of the clinical use of the first tyrosine kinase inhibitor (TKI), imatinib, for chronic myeloid leukemia. Since then, the change in prognosis for patients with this disease is one of the major success stories of modern cancer medicine. The dilemmas that face physicians and patients are no longer only those concerned with delaying inevitable progression to the terminal blastic phase or selecting the individuals most likely to benefit from allogeneic stem-cell transplantation; rather, they are now focused also on the choice of TKI, the management of comorbidities and adverse effects, strategies to improve quality of life, and the appropriateness of a trial of therapy discontinuation...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/30504291/cytotoxic-therapy-in-acute-myeloid-leukemia-not-quite-dead-yet
#13
REVIEW
Laura C Michaelis
Given the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/30503643/compound-mutations-involving-t315i-and-p-loop-mutations-are-the-major-components-of-multiple-mutations-detected-in-tyrosine-kinase-inhibitor-resistant-chronic-myeloid-leukemia
#14
Ki-Hoon Kang, Soo-Hyun Kim, Soo-Young Choi, Hae-Lyun Yoo, Mi-Young Lee, Hye-Young Song, Kyung-Mi Kee, Ji-Hyung Suh, Seon-Young Yang, Eun-Jung Jang, Sung-Eun Lee, Dong-Wook Kim
To analyze the pattern of multiple mutations detected by Sanger sequencing (SS), we performed subcloning sequencing using 218 samples from 45 patients with tyrosine kinase inhibitor resistant chronic myeloid leukemia. At the first time of multiple mutation detection by SS (baseline), a total of 19 major mutations from 45 samples were detected; these mutations were found in the following order: T315I (68.9%), E255 K (33.3%), Y253H (13.3%), G250E (13.3%), and F317 L (11.1%). Subcloning sequencing of 900 baseline colonies identified 556 different mutant types, and 791 among the 900 were colonies with major mutations (87...
November 27, 2018: Leukemia Research
https://www.readbyqxmd.com/read/30502853/increased-cardiovascular-comorbidities-in-patients-with-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia-presenting-with-systemic-inflammatory-and-autoimmune-manifestations
#15
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
https://www.readbyqxmd.com/read/30501735/-crispr-cas9-system-and-its-advances-in-gene-therapy-of-hematologic-diseases-review
#16
Wan-Ying Li, Qing-Ping Gao, Hui Liu
In recent years, with the development of gene editing technology, the site-specific genome can be modified. The curability of genetic disease may be achieved by the use of gene editing techniques. As the simplicity, high specificity and economical efficiency, much attention has been paid to the CRISPR/Cas9 system, which was been widely used in research of molecular biology and other fields of life science. In this review, the mechanism for CR1SPR/Cas9 system and the progress of gene therapy, such as for hemophilia, betathalassaemia and chronic myeloid leukemia were summarized briefly...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/30501698/-relation-between-single-nucleotide-polymorphisms-of-cyp3a5-gene-and-mdr1-gene-loci-and-risk-of-cml-cytogenetic-relapse
#17
Zhang-Yuan Yang, You-Shan Zhang, Cai-Xia Liang, Zheng-Ju Zhou
OBJECTIVE: To analyze the relation between the signle nucleotide polymorphisms (SNP) of CYP3A5 gene and MDR1 gene loci and the risk of cytogenetic relapse in chronic myeloid leukemia (CML). METHODS: The clinical data of 90 patients with CML treated with imatinib in our hospital were collected.The patients were divided into 2 groups: non-relapse and relapse according to relapse and non-relapse, then the relation between the SNP of CYP3A5 gene and MRD1 gene loci and the risk of cytogenetic relapse in CML patients...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/30501399/differential-expression-profiles-and-functional-analysis-of-plasma-mirnas-associated-with-chronic-myeloid-leukemia-phases
#18
Ji Zhang, Yawen Jiang, Xu Han, Mridul Roy, Wenen Liu, Xielan Zhao, Jing Liu
AIM: This study was aimed to investigate the expression profiles and biological function of plasma miRNAs at different phases of chronic myeloid leukemia (CML). MATERIALS & METHODS: Differentially expressed miRNAs were identified by microarray. The candidate miRNAs were validated by quantitative real-time PCR at chronic phase, accelerated phase and blast crisis. The functional analysis of miRNAs was carried out by using DAVID. RESULTS: The putative targets of dysregulated miRNAs were involved in important signaling pathways...
December 3, 2018: Future Oncology
https://www.readbyqxmd.com/read/30498997/the-inflammatory-function-of-human-iga
#19
REVIEW
Ivo S Hansen, Dominique L P Baeten, Jeroen den Dunnen
The prevailing concept regarding the immunological function of immunoglobulin A (IgA) is that it binds to and neutralizes pathogens to prevent infection at mucosal sites of the body. However, recently, it has become clear that in humans IgA is also able to actively contribute to the initiation of inflammation, both at mucosal and non-mucosal sites. This additional function of IgA is initiated by the formation of immune complexes, which trigger Fc alpha Receptor I (FcαRI) to synergize with various other receptors to amplify inflammatory responses...
November 29, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/30497510/exploring-behaviors-treatment-beliefs-and-barriers-to-oral-chemotherapy-adherence-among-adult-leukemia-patients-in-a-rural-outpatient-setting
#20
C Suzanne Lea, Sulochana Bohra, Tiffanie Moore, Chelsea Passwater, Darla Liles
OBJECTIVE: Adherence to oral chemotherapy is essential for patients with chronic myeloid leukemia (CML) and multiple myeloma (MM) to remain in remission. Few studies have used a Likert-type scale to measure medication adherence in CML and MM patients. We applied a validated treatment adherence tool, the ASK-12 (Adherence Starts with Knowledge® ) survey, which assessed inconvenience and forgetfulness, treatment beliefs, and medication-taking behaviors recorded on a five-point Likert-type scale at two visits...
November 29, 2018: BMC Research Notes
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