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https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#1
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28890835/ponatinib-as-a-valid-alternative-strategy-in-patients-with-blast-crisis-chronic-myeloid-leukemia-not-eligible-for-allogeneic-stem-cells-transplantation-and-or-conventional-chemotherapy-report-of-a-case
#2
Cristina Bucelli, Daniele Cattaneo, Valeria Ferla, Manuela Zappa, Caterina de Benedittis, Simona Soverini, Alessandra Iurlo
Currently, imatinib and dasatinib are the only tyrosine-kinase inhibitors approved in the US and Europe for the treatment of blast crisis of chronic myeloid leukemia (BC-CML) at diagnosis, while ponatinib is the only inhibitor used in patients bearing T315I mutation. Here we report the case of a 61-year-old man diagnosed with B-cell lymphoid BC-CML, initially treated with imatinib 800 mg day and then with dasatinib 140 mg day because of intolerance. A complete cytogenetic response (CCyR) was achieved at three months; however, three months later a relapse was observed, and the T315I mutation was detected...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28870619/a-causal-bayesian-network-model-of-disease-progression-mechanisms-in-chronic-myeloid-leukemia
#3
Daniel Koch, Robert S Eisinger, Alexander Gebharter
Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system initiated by a single genetic mutation which results in the oncogenic fusion protein Bcr-Abl. Untreated, patients pass through different phases of the disease beginning with the rather asymptomatic chronic phase and ultimately culminating into blast crisis, an acute leukemia resembling phase with a very high mortality. Although many processes underlying the chronic phase are well understood, the exact mechanisms of disease progression to blast crisis are not yet revealed...
September 1, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28776669/hypomethylation-mediated-h19-overexpression-increases-the-risk-of-disease-evolution-through-the-association-with-bcr-abl-transcript-in-chronic-myeloid-leukemia
#4
Jing-Dong Zhou, Jiang Lin, Ting-Juan Zhang, Ji-Chun Ma, Xi-Xi Li, Xiang-Mei Wen, Hong Guo, Zi-Jun Xu, Zhao-Qun Deng, Wei Zhang, Jun Qian
Previous study has revealed that H19 expression is required for efficient tumor growth induced by BCR-ABL in chronic myeloid leukemia (CML). Herein, we further determined H19 expression and its clinical implication in patients with CML. H19 expression and methylation were detected by real-time quantitative PCR and real-time quantitative methylation-specific PCR, and then clinical implication of H19 expression was further analyzed. H19 expression was significantly up-regulated in CML patients (P < 0.001)...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28762112/targeted-next-generation-sequencing-identifies-clinically-relevant-mutations-in-patients-with-chronic-neutrophilic-leukemia-at-diagnosis-and-blast-crisis
#5
S E Langabeer, K Haslam, J Kelly, J Quinn, R Morrell, E Conneally
PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients...
July 31, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28698852/acute-megakaryoblastic-blast-crisis-as-a-presentation-manifestation-of-chronic-myelogenous-leukemia
#6
Jenna B Bhattacharya, Richa Gupta, Amit Samadhiya
No abstract text is available yet for this article.
June 2017: Blood Research
https://www.readbyqxmd.com/read/28604385/differential-requirements-for-myeloid-leukemia-ifn-%C3%AE-conditioning-determine-graft-versus-leukemia-resistance-and-sensitivity
#7
Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R Green, John T Harty, Warren D Shlomchik
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28588805/-chronic-myelogenous-leukemia-in-primary-blast-crisis-rather-than-de-novo-bcr-abl1-positive-acute-myeloid-leukemia
#8
Cedric Pastoret, Roch Houot
Differentiating chronic myelogenous leukemia in primary blast crisis (CML-BC) from de novo BCR-ABL1-positive acute myeloid leukemia (AML) is a diagnostic challenge with therapeutic consequences. In our case, a basophilia, the presence of the Philadelphia chromosome in all metaphases and the strict exclusion of molecular hallmarks of AML lead us to retain the diagnosis of CML-BC rather than BCR-ABL1+ AML.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28564659/life-threatening-intracerebral-hemorrhage-in-previously-undiagnosed-acute-t-cell-lymphoblastic-leukemia-with-blast-crisis-a-nightmare-in-neurosurgeon-s-life
#9
Abhay Singh, Rahul Gupta, Devender Chhonker, Gangesh Gunjan, Harjinder Singh Bhatoe
Spontaneous, nontraumatic intracerebral hemorrhage is a significant cause of morbidity and mortality throughout the world. Acute lymphoblastic leukemia is the most common cancer diagnosed in children. According to the literature, only 6 cases of acute lymphoblastic leukemia presenting as intracerebral hemorrhage have been reported. Five out of the 6 patients were managed conservatively; 3 out of these 6 patients survived with correction of coagulopathy. Surgical intervention was performed in only 1 of the previously reported cases in which the patient could not be salvaged...
2017: Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28559151/generic-imatinib-in-chronic-myeloid-leukemia-survival-of-the-cheapest
#10
Madhav Danthala, Sadashivudu Gundeti, Siva Prasad Kuruva, Krishna Chaitanya Puligundla, Praveen Adusumilli, Ashok Pillai Karnam, Stalin Bala, Meher Lakshmi Konatam, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti
INTRODUCTION: The patent expiration of imatinib mesylate (Gleevec; Novartis) on February 1, 2016, has brought the focus back on generic versions of the drug, and an opportunity to provide a safe and cost-effective alternative. The objective of our study was to determine the molecular and cytogenetic responses, survival endpoints (event-free survival, failure-free survival, transformation-free survival, overall survival), and safety of innovator and generic brands of imatinib. MATERIALS AND METHODS: In this retrospective analysis, data from 1812 patients with chronic myeloid leukemia treated with frontline imatinib mesylate (innovator/generic) at a single institution between 2008 and 2014 is included...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28550639/philadelphia-chromosome-positive-acute-myeloid-leukemia-with-masses-and-osteolytic-lesions-finding-of-18f-fdg-pet-ct
#11
Zhan Su, Fengyu Wu, Weiyu Hu, Xiaodan Liu, Shaoling Wu, Xianqi Feng, Zhongguang Cui, Jie Yang, Zhenguang Wang, Hongzai Guan, Hongguo Zhao, Wei Wang, Chunting Zhao, Jun Peng
Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lytic bone lesions...
September 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28523104/3-aroyl-1-4-diarylpyrroles-inhibit-chronic-myeloid-leukemia-cell-growth-through-an-interaction-with-tubulin
#12
Giuseppe La Regina, Ruoli Bai, Antonio Coluccia, Valeria Famiglini, Sara Passacantilli, Valentina Naccarato, Giorgio Ortar, Carmela Mazzoccoli, Vitalba Ruggieri, Francesca Agriesti, Claudia Piccoli, Tiziana Tataranni, Marianna Nalli, Andrea Brancale, Stefania Vultaggio, Ciro Mercurio, Mario Varasi, Concetta Saponaro, Sara Sergio, Michele Maffia, Addolorata Maria Luce Coluccia, Ernest Hamel, Romano Silvestri
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522462/cml-in-blast-crisis-more-common-than-we-think
#13
Stephen P Hunger
No abstract text is available yet for this article.
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28514443/cancer-progression-by-reprogrammed-bcaa-metabolism-in-myeloid-leukaemia
#14
Ayuna Hattori, Makoto Tsunoda, Takaaki Konuma, Masayuki Kobayashi, Tamas Nagy, John Glushka, Fariba Tayyari, Daniel McSkimming, Natarajan Kannan, Arinobu Tojo, Arthur S Edison, Takahiro Ito
Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28504724/single-cell-transcriptomics-uncovers-distinct-molecular-signatures-of-stem-cells-in-chronic-myeloid-leukemia
#15
Alice Giustacchini, Supat Thongjuea, Nikolaos Barkas, Petter S Woll, Benjamin J Povinelli, Christopher A G Booth, Paul Sopp, Ruggiero Norfo, Alba Rodriguez-Meira, Neil Ashley, Lauren Jamieson, Paresh Vyas, Kristina Anderson, Åsa Segerstolpe, Hong Qian, Ulla Olsson-Strömberg, Satu Mustjoki, Rickard Sandberg, Sten Eirik W Jacobsen, Adam J Mead
Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28454232/philadelphia-chromosome-with-acute-myeloid-leukemia-and-concurrent-large-b-cell-lymphoma-of-different-origins-a-case-report
#16
Yang Dai, Xiao Shuai, Pu Kuang, Lin Wang, Ting Liu, Ting Niu
Philadelphia chromosome with de novo acute myeloid leukemia (Ph + AML) arising from t(9;22) is an uncommon occurrence. Ph + AML is known to respond poorly to conventional chemotherapy. To the best of our knowledge, simultaneous diagnosis of de novo Ph + AML and lymphoma in a single patient has not yet been reported. The present study reports the case of a 37-year-old female patient who presented with bone pain, fever and lymphadenopathy, and was diagnosed as Ph + AML with concurrent diffuse large B cell lymphoma...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28452111/epigenetic-dysregulation-of-id4-predicts-disease-progression-and-treatment-outcome-in-myeloid-malignancies
#17
Jing-Dong Zhou, Ting-Juan Zhang, Xi-Xi Li, Ji-Chun Ma, Hong Guo, Xiang-Mei Wen, Wei Zhang, Lei Yang, Yang Yan, Jiang Lin, Jun Qian
Promoter hypermethylation-mediated inactivation of ID4 plays a crucial role in the development of solid tumours. This study aimed to investigate ID4 methylation and its clinical relevance in myeloid malignancies. ID4 hypermethylation was associated with higher IPSS scores, but was not an independent prognostic biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS). However, ID4 hypermethylation correlated with shorter OS and leukaemia-free survival (LFS) time and acted as an independent risk factor affecting OS in acute myeloid leukaemia (AML)...
August 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#18
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444777/interphase-fish-for-bcr-abl1-rearrangement-on-neutrophils-a-decisive-tool-to-discriminate-a-lymphoid-blast-crisis-of-chronic-myeloid-leukemia-from-a-de-novo-bcr-abl1-positive-acute-lymphoblastic-leukemia
#19
Estelle Balducci, Marie Loosveld, Ilhem Rahal, John Boudjarane, Emilie Alazard, Chantal Missirian, Marina Lafage-Pochitaloff, Gérard Michel, Hélène Zattara
Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML...
April 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28416739/tki-rotation-induced-persistent-deep-molecular-response-in-multi-resistant-blast-crisis-of-ph-cml
#20
Peter Valent, Susanne Herndlhofer, Mathias Schneeweiß, Bernd Boidol, Anna Ringler, Stefan Kubicek, Karoline V Gleixner, Gregor Hoermann, Emir Hadzijusufovic, Leonhard Müllauer, Wolfgang R Sperr, Giulio Superti-Furga, Christine Mannhalter
In chronic myeloid leukemia (CML) resistance against one or more BCR-ABL1 tyrosine kinase inhibitors (TKI) remains a clinical challenge. Preclinical data suggest that TKI combinations may overcome resistance. We report on a heavily pre-treated 78 year-old female patient with CML who developed multi-resistant blast crisis with bone marrow fibrosis and a Ph- clone. Treatment with ponatinib resulted in blast cell clearance, decrease in fibrosis, and disappearance of BCR-ABL1, but also in severe thrombocytopenia with bleedings requiring platelet transfusions...
April 4, 2017: Oncotarget
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