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https://www.readbyqxmd.com/read/28866095/differential-expression-of-muc4-gpr110-and-il2ra-defines-two-groups-of-crlf2-rearranged-acute-lymphoblastic-leukemia-patients-with-distinct-secondary-lesions
#1
Teresa Sadras, Susan L Heatley, Chung H Kok, Phuong Dang, Kate M Galbraith, Barbara J McClure, Walter Muskovic, Nicola C Venn, Sarah Moore, Michael Osborn, Tamas Revesz, Andrew S Moore, Timothy P Hughes, David Yeung, Rosemary Sutton, Deborah L White
CRLF2-rearrangements (CRLF2-r) occur frequently in Ph-like B-ALL, a high-risk ALL sub-type characterized by a signaling profile similar to Ph + ALL, however accumulating evidence indicates genetic heterogeneity within CRLF2-r ALL. We performed thorough genomic characterization of 35 CRLF2-r cases (P2RY8-CRLF2 n = 18; IGH-CRLF2 n = 17). Activating JAK2 mutations were present in 34% of patients, and a CRLF2-F232C mutation was identified in an additional 17%. IKZF1 deletions were detected in 63% of cases...
September 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28857648/impact-of-clinical-utility-of-mrd-assessment-with-different-techniques-on-survival-in-acute-b-lymphoblastic-leukemia
#2
Aijie Huang, Chongmei Huang, Gusheng Tang, Hui Cheng, Min Liu, Jing Ding, Shenglan Gong, Qi Chen, Weiping Zhang, Jianmin Yang, Jianmin Wang, Xiaoxia Hu
We investigated the impact of minimal residual disease (MRD) obtained from different approaches on the outcomes of 141 B lymphoblastic leukemia (B-ALL) patients. Among 169 samples with more than 5% blasts by morphology, 3.6% (6/169) were Flow-MRD negative. Of the 212 positive molecular-MRD samples from Ph+ ALL patients, 55 (25.9%) were Flow-MRD negative. Before consolidation or allogeneic stem cell transplantation (allo-HSCT), negative Flow-MRD was associated with improved survival (p = .019 and .041, respectively) for Ph- ALL patients, but not for Ph+ ALL (p = ...
August 31, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28854975/ruxolitinib-nilotinib-cotreatment-inhibits-leukemia-propagating-cells-in-philadelphia-chromosome-positive-all
#3
Yuan Kong, Yi-Lin Wu, Yang Song, Min-Min Shi, Xie-Na Cao, Hong-Yan Zhao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang
BACKGROUND: As one of the major treatment obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL), relapse of Ph(+)ALL may result from the persistence of leukemia-propagating cells (LPCs). Research using a xenograft mouse assay recently determined that LPCs were enriched in the CD34(+)CD38(-)CD58(-) fraction in human Ph(+)ALL. Additionally, a cohort study demonstrated that Ph(+)ALL patients with a LPCs phenotype at diagnosis exhibited a significantly higher cumulative incidence of relapse than those with the other cell phenotypes even with uniform front-line imatinib-based therapy pre- and post-allotransplant, thus highlighting the need for novel LPCs-based therapeutic strategies...
August 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28839124/biochemical-phosphates-observed-using-hyperpolarized-31-p-in-physiological-aqueous-solutions
#4
Atara Nardi-Schreiber, Ayelet Gamliel, Talia Harris, Gal Sapir, Jacob Sosna, J Moshe Gomori, Rachel Katz-Brull
The dissolution-dynamic nuclear polarization technology had previously enabled nuclear magnetic resonance detection of various nuclei in a hyperpolarized state. Here, we show the hyperpolarization of (31)P nuclei in important biological phosphates (inorganic phosphate and phosphocreatine) in aqueous solutions. The hyperpolarized inorganic phosphate showed an enhancement factor >11,000 (at 5.8 T, 9.3% polarization) in D2O (T1 29.4 s). Deuteration and the solution composition and pH all affected the lifetime of the hyperpolarized state...
August 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28781850/t315i-clone-selection-in-a-ph-all-patient-under-low-dose-ponatinib-maintenance
#5
Jasmine Noetzli, Mathilde Gavillet, Stavroula Masouridi-Levrat, Michel Duchosal, Olivier Spertini
We report here the clinical course of a Ph+ ALL patient who was treated with ponatinib 15 mg/day, as maintenance therapy, and developed a BCR-ABL T315I mutation leading to ALL relapse. This clonal evolution was reversed, without adverse effects, by increasing ponatinib to 45 mg/day. To our knowledge, we have been confronted with the first clinical case of a T315I clonal selection of ALL caused by subeffective therapeutic level of the drug. This single patient experience highlights the risk of T315I clone selection in Ph+ ALL treated with reduced dose ponatinib...
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28752758/engineering-of-yersinia-phytases-to-improve-pepsin-and-trypsin-resistance-and-thermostability-and-application-potential-in-the-food-and-feed-industry
#6
Canfang Niu, Peilong Yang, Huiying Luo, Huoqing Huang, Yaru Wang, Bin Yao
Susceptibility to proteases usually limits the application of phytase. We sought to improve the pepsin and trypsin resistance of YeAPPA from Yersinia enterocolitica and YkAPPA from Y. kristensenii by optimizing amino acid polarity and charge. The predicted pepsin/trypsin cleavage sites F89/K226 in pepsin/trypsin-sensitive YeAPPA and the corresponding sites (F89/E226) in pepsin-sensitive but trypsin-resistant YkAPPA were substituted with S and H, respectively. Six variants were produced in Pichia pastoris for catalytic and biochemical characterization...
August 30, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#7
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28711932/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#8
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28668978/prognostic-value-of-tricuspid-regurgitation-velocity-and-probability-of-pulmonary-hypertension-in-patients-undergoing-transcatheter-aortic-valve-implantation
#9
Pawel Kleczynski, Artur Dziewierz, Agata Wiktorowicz, Maciej Bagienski, Lukasz Rzeszutko, Danuta Sorysz, Jaroslaw Trebacz, Robert Sobczynski, Marek Tomala, Dariusz Dudek
Pulmonary hypertension (PH) is associated with adverse clinical outcomes after transcatheter aortic valve implantation (TAVI). We sought to investigate the effects of tricuspid regurgitant velocity (TRV) and echocardiographic probability of PH on clinical outcomes of patients undergoing TAVI. A total of 148 consecutive patients undergoing TAVI were included and stratified as having "low" (TRV ≤2.8 m/s), "intermediate" (TRV 2.9-3.4 m/s), and "high" (TRV >3.4 m/s) probability of PH. Only the patients from the "high" probability group were considered as patients with PH...
July 1, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28654842/haploidentical-hematopoietic-stem-cell-transplantation-for-pediatric-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-the-imatinib-era
#10
Huan Chen, Kai-Yan Liu, Lan-Ping Xu, Yu-Hong Chen, Xiao-Hui Zhang, Yu Wang, Ya-Zhen Qin, Yan-Rong Liu, Yue-Yun Lai, Xiao-Jun Huang
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important curative option for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who have a poor response to chemotherapy plus imatinib. For such children, if there are no matched related or unrelated donors, alternative donor transplantation may be a choice. The role of haploidentical donor (HID) HSCT in pediatric patients with Ph+ ALL has not been reported. The study population included pediatric patients with Ph+ ALL who underwent HID-HSCT...
August 2017: Leukemia Research
https://www.readbyqxmd.com/read/28652672/independent-predictors-of-developing-pulmonary-hypertension-in-heart-failure-with-reduced-versus-preserved-ejection-fraction
#11
Alaa Roushdy, Walaa Adel
OBJECTIVES: To investigate the different clinical and echocardiographic predictors of evolving PH in patients with heart failure with and without reduced ejection fraction. METHODS AND RESULTS: The study included 153 heart failure patients with reduced ejection fraction (HFrEF) (n = 89) and preserved ejection fraction (HFpEF) (n = 64) both of which were subdivided into 2 subgroups according to the presence of PH. All patients were subjected to detailed clinical assessment and full transthoracic echocardiogram...
July 2017: Journal of the Saudi Heart Association
https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#12
Peter M Alexander, David L Caudell, Gregory L Kucera, Kristin M Pladna, Timothy S Pardee
Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable...
2017: PloS One
https://www.readbyqxmd.com/read/28641629/-ratio-of-primary-bone-marrow-cells-after-induction-chemothrapy-for-two-weeks-in-the-patients-with-ph-all-and-its-influence-on-complete-remission-and-overall-progrosis
#13
Xi-Feng Wu, Ling Sun, Tan-Tan Li, Xiang-Cong Yin, Xue-Hong Ran
OBJECTIVE: To investigate the influence of bone marrow blasts ratio after induction chemotherapy for 2 weeks in patients with Ph(-) ALL, and it's influence on complete remission (CR) and overall prognosis. METHODS: A total of 172 patients with Ph(-) ALL in our hospital from March 2012 to February 2016 were selected. The bone marrow blast ratio was analyzed by the receiver-operating characteristic curve (ROC) in patients after induction chemotherapy for 2 weeks, at same time its influence on CR and overall prognosis of Ph(-) ALL patients was evaluated...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28616912/-the-roles-of-glut5-in-imatinib-resistance-in-the-ph-acute-lymphoblastic-leukemia-cell
#14
Tian-You Yan, Duo-Lan Naren, Yu-Ping Gong
OBJECTIVES: To explore the possible roles of glucose transport 5 (Glut5) in imatinib resistance in the Ph(+) acute lymphoblastic leukemia cell (Ph(+) ALL). METHODS: The gene chip technique was used to detect different gene expression between Ph(+) ALL cell line SUP-B15/R (imatinib resistant cell line) and SUP-B15/S (imatinib sensitive cell line), the gene of solute carrier family 2 member 5 (SLC2A5) and its coded protein Glut5 were screened out and were reconfirmed by qPCR and Western blot assay...
May 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28612529/-the-mechanism-of-combination-using-mtorc1-2-inhibitor-and-imatinib-to-suppress-cell-proliferation-of-ph-all-cell-line
#15
Jia-Hui Wu, Fang-Fang Shi, Yu-Ping Gong, Rui Shi
OBJECTIVES: To investigate the anti-leukemia effect and mechanism of mTORC1/2 inhibitor PP242 combined with imatinib (IM) on the proliferation of Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15. METHODS: SUP-B15 cell line was treated with PP242, imatinib (IM), or PP242 plus IM for 72 h, IC50 values (the concentration of drug required to kill 50% of the cells) and the combination index (CI ) of synergistic cytotoxicity was determined using MTT methods...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28597761/metabolic-and-functional-evaluation-of-the-heart-and-lungs-in-pulmonary-hypertension-by-gated-2-18f-fluoro-2-deoxy-d-glucose-positron-emission-tomography
#16
Didem Saygin, Kristin B Highland, Samar Farha, Margaret Park, Jacqueline Sharp, Emir Charles Roach, W H Wilson Tang, James D Thomas, Serpil C Erzurum, Donald R Neumann, Frank P DiFilippo
Pulmonary hypertension (PH) is associated with a metabolic shift towards glycolysis in both the right ventricle and lung. This results in increased glucose uptake to compensate for the lower energy yield of glycolysis, which creates a potential for 2-[18F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to be a useful tool in the evaluation of participants with PH. We investigated the utility of PET for PH by comparing FDG-PET uptake in the right ventricle and lungs in 30 participants with PH and eight healthy controls and correlating these measurements with echocardiographic (ECHO) measurements and other traditional assessments commonly used in PH...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28592975/prognostic-factors-and-treatment-of-pediatric-acute-lymphoblastic-leukemia
#17
REVIEW
Jae Wook Lee, Bin Cho
The event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL) has shown remarkable improvement in the past several decades. In Korea also, a recent study showed 10-year EFS of 78.5%. Much of the improved outcome for pediatric ALL stems from the accurate identification of prognostic factors, the designation of risk group based on these factors, and treatment of appropriate duration and intensity according to risk group, done within the setting of cooperative clinical trials. The schema of first-line therapy for ALL remains mostly unchanged, although many groups have now reported on the elimination of cranial irradiation in all patients with low rates of central nervous system relapse...
May 2017: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28562755/evaluating-respiratory-musculature-quality-of-life-anxiety-and-depression-among-patients-with-indeterminate-chronic-chagas-disease-and-symptoms-of-pulmonary-hypertension
#18
Alícia Cristina Suman, Érika Alessandra Pellison Nunes da Costa, Silméia Garcia Zanati Bazan, João Carlos Hueb, Fabio Cardoso de Carvalho, Luis Cuadrado Martin, Hugo Hyung Bok Yoo
INTRODUCTION: Chagas disease (CD) is progressive and incapacitating, especially when cardiopulmonary function is affected. For example, respiratory muscle weakness can cause dyspnea upon exertion and fatigue, which may be exacerbated when it is associated with pulmonary hypertension (PH). The present study aimed to evaluate respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic CD and symptoms of PH. METHODS: All individuals completed a clinical evaluation, spirometry, a 6-min walking test, respiratory musculature testing using maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax), the Hospital Anxiety and Depression Scale, and the SF-36 questionnaire...
March 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#19
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
August 2017: Leukemia Research
https://www.readbyqxmd.com/read/28539032/elevated-gastric-antrum-erosions-in-portal-hypertension-patients-peptic-disease-or-mucosal-congestion
#20
Fernanda Cordeiro de Azevedo Conejo, Mabel Tatty Medeiros Fracassi, Maurício Saab Assef, Maurício Alves Ribeiro, Luiz Arnaldo Szutan, Fabio Gonçalves Ferreira
Background/Aims: Portal hypertension (PH) is a syndrome characterized by chronic increase in the pressure gradient between the portal vein and inferior vena cava. Previous studies have suggested an increased frequency of antral elevated erosive gastritis in patients with PH, as well as an etiologic association; however, there has not been any histological evidence of this hypothesis to date. Our aim was to evaluate the histological features found in elevated antral erosions in patients with portal hypertension...
May 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
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