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https://www.readbyqxmd.com/read/28295161/magnesium-and-molecular-crowding-of-the-cosolutes-stabilize-the-i-motif-structure-at-physiological-ph
#1
Sarika Saxena, Savita Joshi, J Shankaraswamy, Shikhar Tyagi, Shrikant Kukreti
Most of the important genomic regions, especially the G,C rich gene promoters, consist of sequences with potential to form G,C-tetraplexes on both the DNA strands. In the present study, we used three C-rich oligonucleotides (11Py, 21Py and HTPy), of which 11Py and 21Py are located at various transcriptional regulatory elements of the human genome while HTPy sequence is a C-rich strand of human telomere sequence. These C-rich oligonucleotides formed i-motif structures, verified by Circular Dichroism (CD), UV absorption melting experiments, and native gel electrophoresis...
March 14, 2017: Biopolymers
https://www.readbyqxmd.com/read/28271596/team-based-approach-to-identify-cardiac-toxicity-in-critically-ill-hematopoietic-stem-cell-transplant-recipients
#2
Christopher E Dandoy, Sonata Jodele, Zachary Paff, Russel Hirsch, Thomas D Ryan, John L Jefferies, Michelle Cash, Seth Rotz, Abigail Pate, Michael D Taylor, Javier El-Bietar, Kasiani C Myers, Gregory Wallace, Adam Nelson, Michael Grimley, Thomas Pfeiffer, Adam Lane, Stella M Davies, Ranjit S Chima
INTRODUCTION: We observed pulmonary hypertension (PH), pericardial effusions, and left ventricular systolic dysfunction (LVSD) in multiple critically ill hematopoietic stem cell transplant (HSCT) recipients. We implemented routine structured echocardiography screening for HSCT recipients admitted to the pediatric intensive care unit (PICU) using a standardized multidisciplinary process. METHODS: HSCT recipients admitted to the PICU with respiratory distress, hypoxia, shock, and complications related to transplant-associated thrombotic microangiopathy were screened on admission and every 1-2 weeks thereafter...
March 8, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28184964/absorption-metabolism-and-excretion-of-14-c-ponatinib-after-a-single-oral-dose-in-humans
#3
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...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28032244/dasatinib-a-review-in-chronic-myeloid-leukaemia-and-ph-acute-lymphoblastic-leukaemia
#4
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/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#5
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27935576/acute-lymphoblastic-leukemia-relapsing-after-first-line-pediatric-inspired-therapy-a-retrospective-graall-study
#6
A Desjonquères, P Chevallier, X Thomas, F Huguet, T Leguay, M Bernard, J-O Bay, E Tavernier, A Charbonnier, F Isnard, M Hunault, P Turlure, M Renaud, J-N Bastié, C Himberlin, S Lepretre, B Lioure, V Lhéritier, V Asnafi, K Beldjord, M Lafage-Pochitaloff, M C Béné, N Ifrah, H Dombret
The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8...
December 9, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#7
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
Although the emergence of bone marrow (BM)-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and using them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#8
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890258/should-anyone-with-philadelphia-chromosome-positive-all-who-is-negative-for%C3%A2-minimal-residual-disease-receive-a-hematopoietic-stem-cell-transplant-in-first-remission
#9
REVIEW
Mark R Litzow
Outcomes for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in the pre-imatinib era were poor, particularly if patients did not receive an allogeneic hematopoietic stem cell transplant. This led to the recommendation that all patients with Ph+ ALL, if they were transplant candidates, should be transplanted. With the introduction of imatinib and subsequently other tyrosine kinase inhibitors, patient outcomes improved dramatically, raising the question of whether transplant in first complete molecular remission for these patients is really necessary...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#10
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in%C3%A2-b-progenitor-acute-lymphoblastic-leukemia
#11
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high-risk B-progenitor acute lymphoblastic leukemia (ALL), such as BCR-ABL1-positive (Ph+) and Ph-like ALL, and are associated with poor outcome even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiation, skewing lineage of leukemia from myeloid to lymphoid, and, in Ph+ leukemia, conferring resistance to tyrosine kinase inhibitor (TKI) therapy without abrogating ABL1 inhibition...
February 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27835591/celecoxib-inhibits-proliferation-and-survival-of-chronic-myelogeous-leukemia-cml-cells-via-ampk-dependent-regulation-of-%C3%AE-catenin-and-mtorc1-2
#12
Beatrice Riva, Marco De Dominici, Ilaria Gnemmi, Samanta A Mariani, Alberto Minassi, Valentina Minieri, Paolo Salomoni, Pier Luigi Canonico, Armando A Genazzani, Bruno Calabretta, Fabrizio Condorelli
CML is effectively treated with tyrosine kinase inhibitors (TKIs). However, the efficacy of these drugs is confined to the chronic phase of the disease and development of resistance to TKIs remains a pressing issue. The anti-inflammatory COX2 inhibitor celecoxib has been utilized as anti-tumour drug due to its anti-proliferative activity. However, its effects in hematological malignancies, in particular CML, have not been investigated yet. Thus, we tested biological effects and mechanisms of action of celecoxib in Philadelphia-positive (Ph+) CML and ALL cells...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27795512/how-has-the-management-of-ph-acute-lymphoblastic-leukemia-all-changed-over-the-years
#13
Sabina Chiaretti, Robin Foà
For decades, Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been considered the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL and, in the elderly, it accounts for approximately 50% of cases. The introduction of tyrosine kinase inhibitors (TKIs) has led to obtain complete hematologic remissions (CHR) in virtually all patients, to improve disease-free survival and overall survival, and to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT)...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27788934/meta-analysis-of-outcomes-and-evolution-of-pulmonary-hypertension-before-and-after-transcatheter-aortic-valve-implantation
#14
Mengyao Tang, Xianbao Liu, Chiayu Lin, Yuxin He, Xianlei Cai, Qiyuan Xu, Po Hu, Feng Gao, Jubo Jiang, Xiaoping Lin, Qifeng Zhu, Lihan Wang, Huijia Kong, Yunxian Yu, Jian'an Wang
Pulmonary hypertension (PH) is a common entity in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI), but its role on clinical outcomes remains undetermined. We evaluated the impact of baseline and postprocedural PH on clinical outcomes and changes in pulmonary artery systolic pressure after TAVI by performing a meta-analysis of 16 studies enrolling 9,204 patients with AS who underwent TAVI. In patients with baseline PH, all-cause mortality was significantly increased, as shown by pooled odds ratio (ORs) for overall 30-day (OR 1...
January 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/27786412/initial-testing-of-vs-4718-a-novel-inhibitor-of-focal-adhesion-kinase-fak-against-pediatric-tumor-models-by-the-pediatric-preclinical-testing-program
#15
Raushan T Kurmasheva, Richard Gorlick, E Anders Kolb, Stephen T Keir, John M Maris, Richard B Lock, Hernan Carol, Min Kang, C Patrick Reynolds, Jianrong Wu, Peter J Houghton, Malcolm A Smith
VS-4718, a novel inhibitor of focal adhesion kinase (FAK), was tested against the Pediatric Preclinical Testing Program's (PPTP's) in vitro cell line panel and showed a median relative IC50 of 1.22 μM. VS-4718 was tested in vivo against the PPTP xenograft models using a dose of 50 mg/kg administered by the oral route twice daily for 21 days. VS-4718 induced significant differences in an event-free survival distribution compared with control in 18 of 36 of the evaluable solid tumor xenografts and in 0 of 8 acute lymphoblastic leukemia (ALL) xenografts, but no xenograft lines showed tumor regression...
October 27, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27784350/-establishment-and-identification-of-mouse-model-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#16
Xue Wang, Na Qi, Sha Ma, Xu-Guang Song, Zhi-Ling Yan, Qing-Yun Wu, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To establish a mouse model of Ph(+) acute lymphoblastic leukemia (ALL) for providing a valuable tool to facilitate the researches on Ph(+) ALL. METHODS: CML-like mice were generated by transfection to bone marrow cells of BABL/c with Mig190 retrovirus. The Ph(+) ALL mouse model was established by infusion of sorted CML like mouse-derived BCR-ABL(+) B cells into the mice of same linege. Immonophenotypes, BCR-ABL transcription and expression of these leukemic cells were detected by flow cytometry, RT-PCR and Western blot respectively...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27781393/t-cell-rich-hla-haploidentical-hematopoietic-stem-cell-transplantation-for-relapsed-refractory-pediatric-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-without-posttransplant-tyrosine-kinase-inhibitor-therapy
#17
Hideki Sano, Kazuhiro Mochizuki, Mitsuko Akaihata, Shogo Kobayashi, Hitoshi Ohto, Atsushi Kikuta
Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT...
October 26, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27725845/exosome-mediated-growth-effect-on-the-non-growing-pre-b-acute-lymphoblastic-leukemia-cells-at-low-starting-cell-density
#18
Sapan J Patel, Costel C Darie, Bayard D Clarkson
Tumors contain heterogeneous cell populations and achieve dominance by functioning as collective systems. The mechanisms underlying the aberrant growth and interactions between cells are not very well understood. The pre-B acute lymphoblastic leukemia cells we studied were obtained directly from a patient with Ph+ ALL. A new Ph+ ALL cell line (ALL3) was established from the leukemic cells growing as ascitic cells in his pleural fluid. The patient died of his disease shortly after the cells were obtained. ALL3 cells grow well at high cell densities (HD), but not at low cell densities...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27634020/the-persistence-of-minimal-residual-disease-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-we-know-it-s-bad-now-what
#19
Jessica T Leonard, Wendy Stock
No abstract text is available yet for this article.
November 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27612971/ph-all-cells-are-susceptible-to-dual-targeting-of-bcl2-and-abl-lyn
#20
(no author information available yet)
Dual targeting of the ABL and LYN kinases and BCL2 synergizes to promote Ph(+)ALL cell apoptosis.
October 2016: Cancer Discovery
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