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https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#1
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
#2
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
#3
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...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in-b-progenitor-acute-lymphoblastic-leukemia
#4
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 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 in the treatment of Ph+ ALL. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiating, skewing lineage of leukemia from myeloid to lymphoid, and in Ph+ leukemia, conferring resistance to TKI therapy without abrogating ABL1 inhibition...
November 16, 2016: 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
#5
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
#6
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
#7
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...
September 29, 2016: 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
(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
https://www.readbyqxmd.com/read/27593943/effects-of-different-sewage-sludge-applications-on-heavy-metal-accumulation-growth-and-yield-of-spinach-spinacia-oleracea-l
#14
Ebrahem M Eid, Ahmed F El-Bebany, Sulaiman A Alrumman, Abd El-Latif Hesham, Mostafa A Taher, Khaled F Fawy
In this study, we present the response of spinach to different amendment rates of sewage sludge (0, 10, 20, 30, 40 and 50 g kg(-1)) in a greenhouse pot experiment, where plant growth, biomass and heavy metal uptake were measured. The results showed that sewage sludge application increased soil EC, organic matter, chromium and zinc concentrations and decreased soil pH. All heavy metal concentrations of the sewage sludge were below the permissible limits for land application of sewage sludge recommended by the Council of the European Communities...
September 3, 2016: International Journal of Phytoremediation
https://www.readbyqxmd.com/read/27582059/targeting-bcl-2-and-abl-lyn-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#15
Jessica T Leonard, Joelle S J Rowley, Christopher A Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E Spurgeon, Brian J Druker, Jeffrey W Tyner, Bill H Chang
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies...
August 31, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27548716/the-development-of-agents-targeting-the-bcr-abl-tyrosine-kinase-as-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-treatment
#16
Xavier Thomas, Maël Heiblig
In Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL...
November 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27537935/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-is-separated-into-two-subgroups-associated-with-survival-by-bcr-abl-fluorescence-in-situ-hybridization-of-segmented-cell-nuclei-report-from-a-single-institution
#17
Yoshimasa Kamoda, Kiyotaka Izumi, Futoshi Iioka, Takashi Akasaka, Fumihiko Nakamura, Chiyuki Kishimori, Katsuyo Tsuda, Katsuhiro Fukutsuka, Atsuko Okumura, Masahiko Hayashida, Hitoshi Ohno
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-...
2016: Acta Haematologica
https://www.readbyqxmd.com/read/27521363/the-cervicovaginal-microbiota-and-its-associations-with-human-papillomavirus-detection-in-hiv-infected-and-hiv-uninfected-women
#18
Laura L Reimers, Supriya D Mehta, L Stewart Massad, Robert D Burk, Xianhong Xie, Jacques Ravel, Mardge H Cohen, Joel M Palefsky, Kathleen M Weber, Xiaonan Xue, Kathryn Anastos, Howard Minkoff, Jessica Atrio, Gypsyamber D'Souza, Qian Ye, Christine Colie, Christine P Zolnik, Gregory T Spear, Howard D Strickler
BACKGROUND:  Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. METHODS:  16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4(+) T-cell count of > 500 cells/mm(3), and 20 were HIV infected with progressive immunosuppression...
November 1, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27494842/the-photosensitizer-verteporfin-has-light-independent-anti-leukemic-activity-for-ph-positive-acute-lymphoblastic-leukemia-and-synergistically-works-with-dasatinib
#19
Takanobu Morishita, Fumihiko Hayakawa, Keiki Sugimoto, Mizuho Iwase, Hideyuki Yamamoto, Daiki Hirano, Yuki Kojima, Naoto Imoto, Tomoki Naoe, Hitoshi Kiyoi
Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, particularly from the viewpoints of microenvironmental independence. Patient-derived xenografts (PDX) are established by the transfer of primary tumor cells directly from patients into immunodeficient mice and can provide primary-like tumor cells of the amount needed at the desired time. We developed a high-throughput drug screening system using PDX cells and performed drug screening using the PDX cells of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)...
August 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27492792/achieving-molecular-remission-before-allogeneic-stem-cell-transplantation-in-adult-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-impact-on-relapse-and-long-term-outcome
#20
Federico Lussana, Tamara Intermesoli, Francesca Gianni, Cristina Boschini, Arianna Masciulli, Orietta Spinelli, Elena Oldani, Manuela Tosi, Anna Grassi, Margherita Parolini, Ernesta Audisio, Chiara Cattaneo, Roberto Raimondi, Emanuele Angelucci, Irene Maria Cavattoni, Anna Maria Scattolin, Agostino Cortelezzi, Francesco Mannelli, Fabio Ciceri, Daniele Mattei, Erika Borlenghi, Elisabetta Terruzzi, Claudio Romani, Renato Bassan, Alessandro Rambaldi
Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials...
November 2016: Biology of Blood and Marrow Transplantation
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