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https://www.readbyqxmd.com/read/28523104/3-aroyl-1-4-diarylpyrroles-inhibit-chronic-myeloid-leukemia-cell-growth-through-an-interaction-with-tubulin
#1
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
#2
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
#3
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 17, 2017: Nature
https://www.readbyqxmd.com/read/28504724/single-cell-transcriptomics-uncovers-distinct-molecular-signatures-of-stem-cells-in-chronic-myeloid-leukemia
#4
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...
May 15, 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
#5
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
#6
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)...
April 27, 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
#7
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
#8
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
#9
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
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/28356267/hemoglobin-inhibits-albumin-uptake-by-proximal-tubule-cells-implications-for-sickle-cell-disease
#11
Megan L Eshbach, Amandeep Kaur, Youssef Rbaibi, Jesus Tejero, Ora A Weisz
Proximal tubule (PT) dysfunction, including tubular proteinuria, is a significant complication in young sickle cell disease (SCD) that can eventually lead to chronic kidney disease. Hemoglobin (Hb) dimers released from red blood cells upon hemolysis are filtered into the kidney and internalized by megalin/cubilin receptors into PT cells. The PT is especially sensitive to heme toxicity, and tubular dysfunction in SCD is thought to result from prolonged exposure to filtered Hb. Here we show that concentrations of Hb predicted to enter the tubule lumen during hemolytic crisis competitively inhibit the uptake of another megalin/cubilin ligand (albumin) by proximal tubule (PT) cells...
March 29, 2017: American Journal of Physiology. Cell Physiology
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/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#13
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation, remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in granulocyte-macrophage progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
April 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28315428/p53-modulates-the-effect-of-ribosomal-protein-s6-kinase1-s6k1-on-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#14
Ling-Yi Xiao, Wai-Ming Kan
Chronic myeloid leukemia (CML) is characterized by the expression of the oncoprotein, BCR-ABL. BCR-ABL inhibitors revolutionized CML chemotherapy while blast crisis (BC) CML patients are less responsive. Since suppression of ribosomal protein S6 kinase1 (S6K1) phosphorylation reverses the resistance to BCR-ABL inhibitor in CML cells and S6K1 inhibitors augment cisplatin toxicity in lung cancer cells, we speculated that combination of S6K1 inhibitor and cisplatin may be beneficial for eliminating BC CML cells...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28274536/chronic-myelomonocytic-leukemia-blast-crisis-in-a-patient-with-advanced-non-small-cell-lung-cancer-treated-with-egfr-tyrosine-kinase-inhibitors
#15
Hiroaki Ogata, Isamu Okamoto, Goichi Yoshimoto, Teppei Obara, Kayo Ijichi, Eiji Iwama, Taishi Harada, Koichi Akashi, Yoichi Nakanishi
A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis...
March 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28259737/medication-adherence-molecular-monitoring-and-clinical-outcomes-in-patients-with-chronic-myelogenous-leukemia-in-a-large-hmo
#16
Reina Haque, Jiaxiao Shi, Joanie Chung, Xiaoqing Xu, Chantal Avila, Christopher Campbell, Syed A Ahmed, Lei Chen, Joanne E Schottinger
OBJECTIVE: Our objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML). DESIGN: We assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews...
March 1, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28191543/the-third-time-chronic-myeloid-leukemia-in-lymphoblastic-crisis-with-abl1-kinase-mutation-induced-by-decitabine-dexamethason-combined-with-nilotinib-and-dasatinib
#17
Suli Wang, Chun Qiao, Yu Zhu, Wenyi Shen, Guangsheng He, Jianyong Li
Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#18
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28179280/gata-factor-mutations-in-hematologic-disease
#19
REVIEW
John D Crispino, Marshall S Horwitz
GATA family proteins play essential roles in development of many cell types, including hematopoietic, cardiac, and endodermal lineages. The first three factors, GATAs 1, 2, and 3, are essential for normal hematopoiesis, and their mutations are responsible for a variety of blood disorders. Acquired and inherited GATA1 mutations contribute to Diamond-Blackfan anemia, acute megakaryoblastic leukemia, transient myeloproliferative disorder, and a group of related congenital dyserythropoietic anemias with thrombocytopenia...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28129457/tumor-suppressor-gene-methylation-on-the-short-arm-of-chromosome-1-in-chronic-myelogenous-leukemia
#20
Naoki Mori, Mari Ohwashi-Miyazaki, Kentaro Yoshinaga, Michiko Okada, Masayuki Shiseki, Toshiko Motoji, Junji Tanaka
OBJECTIVES: We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia (CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML. METHODS: We performed methylation-specific PCR (MS-PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS-PCR, PCR-single-strand conformation polymorphism, and real-time reverse transcriptase PCR were also analyzed...
January 27, 2017: European Journal of Haematology
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