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https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#1
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415816/targeting-the-pim-protein-kinases-for-the-treatment-of-a-t-cell-acute-lymphoblastic-leukemia-subset
#2
Sathish K R Padi, Libia A Luevano, Ningfei An, Ritu Pandey, Neha Singh, Jin H Song, Jon C Aster, Xue-Zhong Yu, Shikhar Mehrotra, Andrew S Kraft
New approaches are needed for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission with chemotherapy. Analysis of the effects of pan-PIM protein kinase inhibitors on human T-ALL cell lines demonstrated that the sensitive cell lines expressed higher PIM1 protein kinase levels, whereas T-ALL cell lines with NOTCH mutations tended to have lower levels of PIM1 kinase and were insensitive to these inhibitors. NOTCH-mutant cells selected for resistance to gamma secretase inhibitors developed elevated PIM1 kinase levels and increased sensitivity to PIM inhibitors...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410239/homoharringtonine-suppresses-imatinib-resistance-via-the-bcl-6-p53-pathway-in-chronic-myeloid-leukemia-cell-lines
#3
Qian Wang, Wei Ding, Yihan Ding, Jingjing Ma, Zhaoye Qian, Jingxian Shao, Yufeng Li
BACKGROUND: The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo. RESULTS: Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410182/parent-and-health-care-provider-perceptions-for-development-of-a-web-based-weight-management-program-for-survivors-of-pediatric-acute-lymphoblastic-leukemia-a-mixed-methods-study
#4
Sara Folta, Winnie Chang, Rachel Hill, Michael Kelly, Susan Meagher, W Paul Bowman, Fang Fang Zhang
BACKGROUND: Survivors of pediatric acute lymphoblastic leukemia (ALL) may experience unhealthy weight gain during treatment, which has been associated with higher risk for chronic health issues. OBJECTIVE: The purpose of this study was to obtain feedback on weight management in pediatric ALL survivors and on the content and implementation of a Web-based weight management program. METHODS: Study participants included 54 parent survey respondents and 19 pediatric oncology professionals in 4 focus groups...
February 9, 2017: JMIR Cancer
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#5
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28405516/assessment-of-tumor-infiltrating-tcrv%C3%AE-9v%C3%AE-2-%C3%AE-%C3%AE-lymphocyte-abundance-by-deconvolution-of-human-cancers-microarrays
#6
Marie Tosolini, Frédéric Pont, Mary Poupot, François Vergez, Marie-Laure Nicolau-Travers, David Vermijlen, Jean-Emmanuel Sarry, Francesco Dieli, Jean-Jacques Fournié
Most human blood γδ cells are cytolytic TCRVγ9Vδ2(+) lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401099/physicians-preferences-and-perceptions-regarding-donor-selection-in-allogeneic-stem-cell-transplantation-in-korea-when-a-matched-domestic-donor-is-not-available
#7
Min Kyung Shin, Sangjin Shin, Ja Youn Lee, Youngil Koh
BACKGROUND: A number of alternative donor options exist for patients who fail to find domestic HLA-matched donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed physicians' perspectives on allo-HSCT donor selection when a matched domestic donor is not available. METHODS: We administered a questionnaire survey to 55 hematologists (response rate: 28%) who attended the annual spring conference of the Korean Society of Haematology in 2015...
March 2017: Blood Research
https://www.readbyqxmd.com/read/28400079/smoking-and-subsequent-risk-of-leukemia-in-japan-the-japan-public-health-center-based-prospective-study
#8
Tomotaka Ugai, Keitaro Matsuo, Norie Sawada, Motoki Iwasaki, Taiki Yamaji, Taichi Shimazu, Shizuka Sasazuki, Manami Inoue, Shoichiro Tsugane
BACKGROUND: Cigarette smoking has been reported to be associated with an increased risk of leukemia. Most epidemiological evidence on the association between cigarette smoking and leukemia risk is from studies conducted in Western populations, however, and evidence from Asian populations is scarce. METHODS: We conducted a large-scale population-based cohort study of 96,992 Japanese subjects (46,493 men and 50,499 women; age 40-69 years at baseline) with an average 18...
April 8, 2017: Journal of Epidemiology
https://www.readbyqxmd.com/read/28394370/more-chronic-gvhd-and-non-relapse-mortality-after-peripheral-blood-stem-cell-compared-with-bone-marrow-in-hematopoietic-transplantation-for-paediatric-acute-lymphoblastic-leukemia-a-retrospective-study-on-behalf-of-the-ebmt-paediatric-diseases-working-party
#9
M Simonin, A Dalissier, M Labopin, A Willasch, M Zecca, A Mouhab, A Chybicka, A Balduzzi, L Volin, C Peters, P Bader, J-H Dalle
No abstract text is available yet for this article.
April 10, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28387926/overall-survival-with-ponatinib-versus-allogeneic-stem-cell-transplantation-in-philadelphia-chromosome-positive-leukemias-with-the-t315i-mutation
#10
Franck E Nicolini, Grzegorz W Basak, Dong-Wook Kim, Eduardo Olavarria, Javier Pinilla-Ibarz, Jane F Apperley, Timothy Hughes, Dietger Niederwieser, Michael J Mauro, Charles Chuah, Andreas Hochhaus, Giovanni Martinelli, Maral DerSarkissian, Mei Sheng Duh, Lisa J McGarry, Hagop M Kantarjian, Jorge E Cortes
BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted...
April 7, 2017: Cancer
https://www.readbyqxmd.com/read/28371314/temporary-resolution-of-insulin-requirement-in-acquired-partial-lipodystrophy-associated-with-chronic-graft-versus-host-disease
#11
Leslie Kimura, Griselda Alvarez, Ning Li, Anna Pawlikowska-Haddal, Theodore B Moore, Jacqueline Casillas, Kuk-Wha Lee
This is a case presentation describing a high insulin requirement that suddenly resolved in a patient with acute lymphoblastic leukemia treated with stem cell transplantation complicated by chronic graft-versus-host disease. The patient was diagnosed with acquired partial lipodystrophy that did not require alternative therapies such as leptin or insulin-like growth factor 1.
March 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28331056/monitoring-of-childhood-all-using-bcr-abl1-genomic-breakpoints-identifies-a-subgroup-with-cml-like-biology
#12
Lenka Hovorkova, Marketa Zaliova, Nicola C Venn, Kirsten Bleckmann, Marie Trkova, Eliska Potuckova, Martina Vaskova, Jana Linhartova, Katerina Machova Polakova, Eva Fronkova, Walter Muskovic, Jodie E Giles, Peter J Shaw, Gunnar Cario, Rosemary Sutton, Jan Stary, Jan Trka, Jan Zuna
We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, over 20% of children (25% [8/32] with minor and 12.5% [1/8] with Major-BCR-ABL1 variants in the consecutive cohorts) had significantly (>1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28329763/the-allosteric-inhibitor-abl001-enables-dual-targeting-of-bcr-abl1
#13
Andrew A Wylie, Joseph Schoepfer, Wolfgang Jahnke, Sandra W Cowan-Jacob, Alice Loo, Pascal Furet, Andreas L Marzinzik, Xavier Pelle, Jerry Donovan, Wenjing Zhu, Silvia Buonamici, A Quamrul Hassan, Franco Lombardo, Varsha Iyer, Michael Palmer, Giuliano Berellini, Stephanie Dodd, Sanjeev Thohan, Hans Bitter, Susan Branford, David M Ross, Timothy P Hughes, Lilli Petruzzelli, K Gary Vanasse, Markus Warmuth, Francesco Hofmann, Nicholas J Keen, William R Sellers
Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR-ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28320465/reduced-microbial-diversity-in-adult-survivors-of-childhood-acute-lymphoblastic-leukemia-and-microbial-associations-with-increased-immune-activation
#14
Ling Ling Chua, Reena Rajasuriar, Mohamad Shafiq Azanan, Noor Kamila Abdullah, Mei San Tang, Soo Ching Lee, Yin Ling Woo, Yvonne Ai Lian Lim, Hany Ariffin, P'ng Loke
BACKGROUND: Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) have health problems that persist or develop years after cessation of therapy. These late effects include chronic inflammation-related comorbidities such as obesity and type 2 diabetes, but the underlying cause is poorly understood. RESULTS: We compared the anal microbiota composition of adult survivors of childhood ALL (N = 73) with healthy control subjects (N = 61)...
March 20, 2017: Microbiome
https://www.readbyqxmd.com/read/28314854/common-nonmutational-notch1-activation-in-chronic-lymphocytic-leukemia
#15
Giulia Fabbri, Antony B Holmes, Mara Viganotti, Claudio Scuoppo, Laura Belver, Daniel Herranz, Xiao-Jie Yan, Yasmine Kieso, Davide Rossi, Gianluca Gaidano, Nicholas Chiorazzi, Adolfo A Ferrando, Riccardo Dalla-Favera
Activating mutations of NOTCH1 (a well-known oncogene in T-cell acute lymphoblastic leukemia) are present in ∼4-13% of chronic lymphocytic leukemia (CLL) cases, where they are associated with disease progression and chemorefractoriness. However, the specific role of NOTCH1 in leukemogenesis remains to be established. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ∼50% of peripheral blood CLL cases lacking gene mutations. We identify a "NOTCH1 gene-expression signature" in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28296681/adenovirus-hepatitis-clinicopathologic-analysis-of-12-consecutive-cases-from-a-single-institution
#16
Kurt B Schaberg, Neeraja Kambham, Richard K Sibley, John P T Higgins
Adenoviruses are common pathogens that usually cause self-limited infections. However, in the immunocompromised host they can cause severe infections involving multiple organs including the liver. A search of the pathology database at Stanford University Medical Center (1995 to 2016) identified 12 cases of adenovirus hepatitis including biopsy and autopsy specimens. There were 8 pediatric patients, 7 of which had received orthotropic liver transplants and 1 of which was receiving chemotherapy for lymphoblastic leukemia...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28282510/cxcr4-cd184-expression-on-stem-cell-harvest-and-cd34-cells-post-transplant
#17
Inas Asfour, Hanaa Afify, Shaza Elkourashy, Maryse Ayoub, Gihan Kamal, Mary Gamal, Ghada Elgohary
OBJECTIVES/BACKGROUND: CXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism. METHODS: This is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014...
March 2, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#18
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28276292/chronic-myelogenous-leukemia-presenting-as-a-secondary-malignancy-after-bcr-abl1-negative-b-lymphoblastic-leukemia-lymphoma-in-a-pediatric-patient
#19
Gheorghe Popa, Cristina Blag, Horatiu Olteanu
Chronic myelogenous leukemia, BCR-ABL1 positive (CML) is a rare myeloproliferative neoplasm in children and presents even less often as a secondary malignancy in the pediatric population. Below, we report a patient with Philadelphia-negative B-lymphoblastic leukemia/lymphoma, who developed CML several years after achieving complete remission, and summarize the existing literature on the clinical and pathologic features of CML as a secondary pediatric malignancy.
January 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#20
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
February 28, 2017: Seminars in Cancer Biology
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