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https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#1
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29742077/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-adults-current-treatments-and-future-perspectives
#2
Musa Yilmaz, Hagop Kantarjian, Farhad Ravandi-Kashani, Nicholas J Short, Elias Jabbour
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs). With the successful incorporation of TKIs into chemotherapy regimens, remissions occur more frequently and patients live longer...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29694642/final-analysis-of-the-jalsg-ph-all202-study-tyrosine-kinase-inhibitor-combined-chemotherapy-for-ph-all
#3
Yoshihiro Hatta, Shuichi Mizuta, Keitaro Matsuo, Shigeki Ohtake, Masako Iwanaga, Isamu Sugiura, Noriko Doki, Heiwa Kanamori, Yasunori Ueda, Chikamasa Yoshida, Nobuaki Dobashi, Tomoya Maeda, Toshiaki Yujiri, Fumihiko Monma, Yoshikazu Ito, Fumihiko Hayakawa, Jin Takeuchi, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe
The Japan Adult Leukemia Study Group (JALSG) Ph+ALL202 study reported a high complete remission (CR) rate for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients treated with imatinib-combined chemotherapy. However, the long-term treatment efficacy remains uncertain. Here, we report a final analysis of the JALSG Ph+ALL202 study. The outcomes were compared with those of the JALSG ALL93 and ALL97 studies, which were conducted in the pre-imatinib era. Ninety-nine newly diagnosed Ph+ALL patients were enrolled in Ph+ALL202 (median age, 45 years; median follow-up, 4...
April 24, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29679774/comparable-results-of-autologous-and-allogeneic-haematopoietic-stem-cell-transplantation-for-adults-with-philadelphia-positive-acute-lymphoblastic-leukaemia-in-first-complete-molecular-remission-an-analysis-by-the-acute-leukemia-working-party-of-the-ebmt
#4
Sebastian Giebel, Myriam Labopin, Michael Potter, Xavier Poiré, Henrik Sengeloev, Gerard Socié, Anne Huynh, Boris V Afanasyev, Urs Schanz, Olle Ringden, Peter Kalhs, Dietrich W Beelen, Antonio M Campos, Tamás Masszi, Jonathan Canaani, Mohamad Mohty, Arnon Nagler
BACKGROUND: Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014...
June 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29665896/-a-modified-protocol-for-rapid-establishing-mouse-model-with-ph-positive-acute-lymphoblastic-leukemia
#5
Na Qi, Xue Wang, Qing-Yun Wu, Zhi-Ling Yan, Lin Wang, Chong Chen, Kai-Lin Xu
OBJECTIVE: To investigate a modified protocol of establishing mouse Ph+ ALL model so as to provide a more convenient and more powerful tool for Ph+ ALL studies. METHODS: Immature B cells from BALB/c mice were transfected with the Mig190 retrovirus and infused into irradiated syngeneic mice. The immunophenotype was identified by flow cytometry, the BCR-ABL was identified by RT-PCR and Western blot. Leukemia cells isolated from sick mice were re-infused into syngeneic mice without irradiation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665256/bcr-abl-enhances-the-prolyl-isomerase-activity-of-pin-1-by-interacting-with-dapk1-in-ph-all
#6
Wen-Bin Cao, Jian-Feng Yao, Si-Zhou Feng, Yi He, Er-Lie Jiang, Rong-Li Zhang, Dong-Lin Yang, Ming Gong, Xiao-Hui Zheng, Shu-Lian Chen, Jia-Li Sun, Lu-Kun Zhou, Ming-Zhe Han
Philadelphia chromosome (Ph)/BCR-ABL-positive (ph+ ) ALL is the most common genetic abnormality associated with ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including ALL, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR-ABL...
April 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29625246/droplet-digital-pcr-is-a-robust-tool-for-monitoring-minimal-residual-disease-in-adult-philadelphia-positive-acute-lymphoblastic-leukemia
#7
Nicoletta Coccaro, Luisa Anelli, Antonella Zagaria, Paola Casieri, Giuseppina Tota, Paola Orsini, Luciana Impera, Angela Minervini, Crescenzio F Minervini, Cosimo Cumbo, Elisa Parciante, Paola Carluccio, Claudia Brunetti, Giorgina Specchia, Francesco Albano
The BCR-ABL1 p190 fusion transcript (m-bcr) is the most frequent variant observed in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). Qualitative-PCR and real-time quantitative PCR are the currently used methods to monitor minimal residual disease (MRD) in Ph+ ALL patients; for the latter, full standardization and an international quality validation are lacking. Here, we developed a droplet digital PCR (ddPCR) assay for MRD monitoring in p190+ ALL cases. The analytical performance was assessed by the limit of detection determination, demonstrating a reliability, sensitivity, and precision of the assay of up to 0...
April 3, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29599144/arf-way-to-ph-all-stratification
#8
Adele K Fielding
No abstract text is available yet for this article.
March 29, 2018: Blood
https://www.readbyqxmd.com/read/29578162/the-autophagy-induced-by-curcumin-via-mek-erk-pathway-plays-an-early-anti-leukemia-role-in-human-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-sup-b15-cells
#9
Yong Guo, Qing Qing Shan, Ping Yu Gong, Sen Chun Wang
Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin has been shown to have inhibitory effects on cancers by inducing apoptosis and autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR, ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph+ ALL cells. Experiments here, were conducted to determine whether autophagy via MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph+ ALL...
2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29575541/simultaneous-detection-of-abl1-mutation-and-ikzf1-deletion-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-using-a-customized-target-enrichment-system-panel
#10
M Aoe, H Ishida, T Matsubara, S Karakawa, H Kawaguchi, K Fujiwara, K Kanamitsu, K Washio, K Okada, M Shibakura, A Shimada
INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary...
March 25, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29572111/comparative-analysis-of-flow-cytometry-and-rq-pcr-for-the-detection-of-minimal-residual-disease-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-after-hematopoietic-stem-cell-transplantation
#11
Xiangyu Zhao, Xiaosu Zhao, Huan Chen, Yazhen Qin, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Xiaojun Huang, Yingjun Chang
The aim of this study was to examine the value of MRD detection by multiparameter flow cytometry (MFC) and RQ-PCR at the early stage after hematopoietic stem cell transplantation (HSCT) for predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome-positive ALL (Ph+-ALL). Patients who maintained complete molecular remission (CMR, BCR/ABL<0.01%) status at 1 and 3 months were associated with a lower relapse rate (P=0.02 and <0.001) and better LFS (P=0.014 and 0.013) than those without a CMR...
March 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29568367/the-new-allosteric-inhibitor-asciminib-is-susceptible-to-resistance-mediated-by-abcb1-and-abcg2-overexpression-in-vitro
#12
Laura N Eadie, Verity A Saunders, Susan Branford, Deborah L White, Timothy P Hughes
Asciminib (previously ABL001), which binds the myristate-binding pocket of the Bcr-Abl kinase domain, is in phase I clinical trials as monotherapy and in combination with imatinib, nilotinib and dasatinib for the treatment of patients with refractory CML or Ph+ ALL. Asciminib sensitivity was evaluated in asciminib naïve BCR-ABL1+ cell lines K562 (negligible ABCB1/ABCG2 expression), K562-Dox (ABCB1-overexpressing through doxorubicin exposure) and K562-ABCG2 (ABCG2 overexpression via transduction) with results demonstrating asciminib efflux by both ABCB1 and ABCG2 transporters...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29562467/-prognostic-factors-of-pediatric-patients-with-ph-positive-acute-lymphoblastic-leukemia
#13
Y J Xue, J Wu, Y X Zuo, Y P Jia, A D Lu, L P Zhang
Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29562444/-efficacy-comparison-of-sequential-treatment-with-first-line-administration-of-second-generation-and-first-generation-tyrosine-kinase-inhibitors-in-patients-with-ph-acute-lymphoblastic-leukemia-followed-by-allogeneic-hematopoietic-stem-cell-transplantation
#14
F Yang, W Z Cai, X D Yang, S N Chen, X W Tang, A N Sun, D P Wu, W Q Qian, H Y Qiu
Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph+ ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29519619/efficacy-of-ponatinib-versus-earlier-generation-tyrosine-kinase-inhibitors-for-front-line-treatment-of-newly-diagnosed-philadelphia-positive-acute-lymphoblastic-leukemia
#15
Elias Jabbour, Maral DerSarkissian, Mei Sheng Duh, Nora McCormick, Wendy Y Cheng, Lisa J McGarry, Ariadne Souroutzidis, Hui Huang, Susan O'Brien, Farhad Ravandi, Hagop M Kantarjian
INTRODUCTION: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). PATIENTS AND METHODS: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29502175/ponatinib-for-treating-acute-lymphoblastic-leukaemia-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#16
REVIEW
Matt Stevenson, Abdullah Pandor, Jean Hamilton, John Stevens, Clare Rowntree, Marrissa Martyn-St James, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (Incyte Corporation) of ponatinib (Inclusig® ) to submit evidence of its clinical and cost effectiveness for previously treated Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) and chronic myeloid leukaemia. This paper focusses on Ph+ ALL. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent evidence review group (ERG)...
March 3, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29480454/ponatinib-for-treating-chronic-myeloid-leukaemia-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#17
REVIEW
Abdullah Pandor, Matt Stevenson, John Stevens, Marrissa Martyn-St James, Jean Hamilton, Jenny Byrne, Claudius Rudin, Andrew Rawdin, Ruth Wong
As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig® ; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP)...
February 26, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29474869/in-the-era-of-bcr-abl1-inhibitors-are-we-closing-the-survival-gap-between-allogeneic-hematopoietic-cell-transplantation-and-chemotherapy-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-first-complete-remission
#18
EDITORIAL
https://www.readbyqxmd.com/read/29471521/variable-response-of-nirk-and-nirs-containing-denitrifier-communities-to-long-term-ph-manipulation-and-cultivation
#19
Miriam B Herold, Madeline E Giles, Colin J Alexander, Elizabeth M Baggs, Tim J Daniell
Denitrification is a key process responsible for the majority of soil nitrous oxide (N2O) emissions but the influences of pH and cultivation on the soil denitrifier community remain poorly understood. We hypothesised that the abundance and community structure of the total bacterial community and bacterial denitrifiers would be pH sensitive and that nirK and nirS containing denitrifiers would differ in their responses to change in pH and cultivation. We investigated the effect of long-term pH-adjusted soils (ranging from pH 4...
April 1, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29429020/leukemia-propagating-cells-demonstrate-distinctive-gene-expression-profiles-compared-with-other-cell-fractions-from-patients-with-de-novo-philadelphia-chromosome-positive-all
#20
COMPARATIVE STUDY
Hong-Yan Zhao, Yang Song, Xie-Na Cao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Yuan Kong
Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph+ ALL. Using a xenograft assay, LPCs enrichment in the CD34+ CD38- CD58- fraction in Ph+ ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph+ ALL. However, little is known about the potential molecular mechanism of LPCs-mediated relapse...
May 2018: Annals of Hematology
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