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Chronic myeloid leukemia

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https://www.readbyqxmd.com/read/29905937/iron-overload-in-patients-with-myelodysplastic-syndromes-an-updated-overview
#1
REVIEW
Nour M Moukalled, Fuad A El Rassi, Sally N Temraz, Ali T Taher
Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS...
June 15, 2018: Cancer
https://www.readbyqxmd.com/read/29902707/antimalarial-drugs-trigger-lysosome-mediated-cell-death-in-chronic-lymphocytic-leukemia-cll-cells
#2
Subhadip Das, Rebecca Dielschneider, Aaron Chanas-LaRue, James B Johnston, Spencer B Gibson
Lysosomes are the most acidic vesicles within mammalian cells and are promising targets for the treatment of breast cancer, glioblastomas and acute myeloid leukemia (AML). Our previous studies have shown that chronic lymphocytic leukemia (CLL) cells are also sensitive to lysosome disruption and cell death, by siramesine or chemotherapy. In the present study, we screened the antimalarial drugs, mefloquine, atovaquone, primaquine, and tafenoquine, for their effects on lysosome disruption and cytotoxicity in primary CLL cells...
June 7, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29902552/exploring-the-major-cross-talking-edges-of-competitive-endogenous-rna-networks-in-human-chronic-and-acute-myeloid-leukemia
#3
Kamalika Sen, Dhananjay Bhattacharyya, Arijita Sarkar, Jyotirmoy Das, Nilanjana Maji, Moitri Basu, Zhumur Ghosh, Tapash Chandra Ghosh
BACKGROUND: Human Chronic and Acute Myeloid Leukemia are myeloproliferative disorders in myeloid lineage of blood cells characterized by accumulation of aberrant white blood cells. In cancer, the anomalous transcriptome includes deregulated expression of non-coding RNAs in conjunction with protein-coding mRNAs in human genome. The coding or non-coding RNA transcripts harboring miRNA-binding sites can converse with and regulate each other by explicitly contending for a limited pool of shared miRNAs and act as competitive endogenous RNAs (ceRNAs)...
June 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29902246/validated-uplc-ms-ms-method-for-the-quantification-of-dasatinib-in-plasma-application-to-pharmacokinetic-interaction-studies-with-nutraceuticals-in-wistar-rats
#4
Hadir M Maher, Nourah Z Alzoman, Shereen M Shehata, Norah O Abanmy
Dasatinib (DAS) is a tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia and in the management of ulcerative colitis (UC). Since some nutraceuticals (e.g. curcumin, olive oil, and cocoa extract) could alter the function of ABC transporters and /or CYP450 enzymes, DAS bioavailability could potentially be affected following their co-administration. This work aims at studying the possibility of PK interaction between DAS and the selected nutraceuticals in UC rats using UPLC- MS/MS...
2018: PloS One
https://www.readbyqxmd.com/read/29900128/residual-peripheral-blood-cd26-leukemic-stem-cells-in-chronic-myeloid-leukemia-patients-during-tki-therapy-and-during-treatment-free-remission
#5
Monica Bocchia, Anna Sicuranza, Elisabetta Abruzzese, Alessandra Iurlo, Santina Sirianni, Antonella Gozzini, Sara Galimberti, Lara Aprile, Bruno Martino, Patrizia Pregno, Federica Sorà, Giulia Alunni, Carmen Fava, Fausto Castagnetti, Luca Puccetti, Massimo Breccia, Daniele Cattaneo, Marzia Defina, Olga Mulas, Claudia Baratè, Giovanni Caocci, Simona Sica, Alessandro Gozzetti, Luigiana Luciano, Monica Crugnola, Mario Annunziata, Mario Tiribelli, Paola Pacelli, Ilaria Ferrigno, Emilio Usala, Nicola Sgherza, Gianantonio Rosti, Alberto Bosi, Donatella Raspadori
Chronic myeloid leukemia (CML) patients in sustained "deep molecular response" may stop TKI treatment without disease recurrence; however, half of them lose molecular response shortly after TKI withdrawing. Well-defined eligibility criteria to predict a safe discontinuation up-front are still missing. Relapse is probably due to residual quiescent TKI-resistant leukemic stem cells (LSCs) supposedly transcriptionally low/silent and not easily detectable by BCR-ABL1 qRT-PCR. Bone marrow Ph+ CML CD34+ /CD38- LSCs were found to specifically co-express CD26 (dipeptidylpeptidase-IV)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29899861/deregulation-of-calcium-homeostasis-in-bcr-abl-dependent-chronic-myeloid-leukemia
#6
Hélène Cabanas, Thomas Harnois, Christophe Magaud, Laëtitia Cousin, Bruno Constantin, Nicolas Bourmeyster, Nadine Déliot
Background: Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the bcr-abl chimeric oncogene, encoding a 210 kDa protein with constitutive tyrosine kinase activity. In spite of the efficiency of tyrosine kinase inhibitors (TKI; Imatinib), other strategies are explored to eliminate CML leukemia stem cells, such as calcium pathways. Results: In this work, we showed that Store-Operated Calcium Entry (SOCE) and thrombin induced calcium influx were decreased in Bcr-Abl expressing 32d cells (32d-p210)...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899829/inhibition-of-fas-associated-phosphatase-1-fap1-facilitates-apoptosis-of-colon-cancer-stem-cells-and-enhances-the-effects-of-oxaliplatin
#7
Weiqi Huang, Ling Bei, Elizabeth A Eklund
Fas associated phosphatase 1 (Fap1) is a ubiquitously expressed protein tyrosine phosphatase. Fap1 substrates include Fas and Gsk3β, suggesting a role in regulating cell survival. Consistent with this, increased Fap1 expression is associated with resistance to Fas or platinum induced apoptosis in some human colon cancer tumors or cell lines. In the current studies, we found that Fap1 expression was significantly greater in CD133+ colon cancer stem cells compared to CD133- tumor cells. PTPN13 promoter activity (encoding Fap1) was repressed by interferon regulatory factor 2 (irf2), and expression of Fap1 and Irf2 were inversely correlated in CD133+ or CD133- colon cancer cells...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899828/efficient-lysis-of-b-chronic-lymphocytic-leukemia-cells-by-the-plant-derived-sesquiterpene-alcohol-%C3%AE-bisabolol-a-dual-proapoptotic-and-antiautophagic-agent
#8
Antonella Rigo, Isacco Ferrarini, Angela Bonalumi, Cristina Tecchio, Alessio Montresor, Carlo Laudanna, Fabrizio Vinante
The sesquiterpene α-bisabolol (α-BSB) is a cytotoxic agent against acute leukemia and chronic myeloid leukemia cells. Here the profile of α-BSB citotoxicity was evaluated ex vivo in primary mononuclear blood cells isolated from 45 untreated B-chronic lymphocytic leukemia (B-CLL) patients. We studied the effects of α-BSB by flow cytometric and western blotting techniques with the following findings: (1) α-BSB was an effective proapoptotic agent against B-CLL cells (IC50 42 ± 15 μM). It was also active, but to a lesser extent, on normal residual B cells and monocytes (IC50 68 ± 34 and 74 ± 28 μM, respectively; p < 0...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29899367/frequent-asxl1-mutations-in-children-and-young-adults-with-chronic-myeloid-leukemia
#9
Thomas Ernst, Melinda Busch, Jenny Rinke, Jana Ernst, Claudia Haferlach, James F Beck, Andreas Hochhaus, Bernd Gruhn
No abstract text is available yet for this article.
June 13, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29896890/clinical-results-according-to-age-in-patients-with-chronic-myeloid-leukemia-receiving-imatinib-frontline-the-younger-the-later-the-worse
#10
Roberto Latagliata, Massimo Breccia, Ida Carmosino, Laura Cesini, Daniela De Benedittis, Sara Mohamed, Federico Vozella, Matteo Molica, Melissa Campanelli, Maria Lucia De Luca, Gioia Colafigli, Luisa Quattrocchi, Maria Giovanna Loglisci, Fulvio Massaro, Martina Canichella, Daniela Diverio, Marco Mancini, Giuliana Alimena, Robin Foà
OBJECTIVES: To evaluate differences in clinical results according to age among patients with chronic myeloid leukemia (CML). METHODS: 207 consecutive CML patients treated with imatinib frontline were revised, dividing them in young adults (>20 <45 years) (YA), middle-aged adults (≥45 <65 years) (MA) and elderly (≥65 years) (EL). RESULTS: Cumulative incidence of complete cytogenetic response (CCyR) and major molecular response (MMolR) were significantly higher in MA compared with YA and EL (p<0...
June 13, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29895969/inhibition-of-maternal-embryonic-leucine-zipper-kinase-with-otssp167-displays-potent-anti-leukemic-effects-in-chronic-lymphocytic-leukemia
#11
Ya Zhang, Xiangxiang Zhou, Ying Li, Yangyang Xu, Kang Lu, Peipei Li, Xin Wang
TP53 pathway defects contributed to therapy resistance and adverse clinical outcome in chronic lymphocytic leukemia (CLL), which represents an unmet clinical need with few therapeutic options. Maternal embryonic leucine zipper kinase (MELK) is a novel oncogene, which plays crucial roles in mitotic progression and stem cell maintenance. OTSSP167, an orally administrated inhibitor targeting MELK, is currently in a phase I/II clinical trial in patients with advanced breast cancer and acute myeloid leukemia. Yet, no investigation has been elucidated to date regarding the oncogenic role of MELK and effects of OTSSP167 in chronic lymphocytic leukemia (CLL)...
June 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29892549/a-case-of-chronic-eosinophilic-leukemia-with-secondary-transformation-to-acute-myeloid-leukemia
#12
Mattias Hofmans, Anke Delie, Karl Vandepoele, Nadine Van Roy, Joni Van der Meulen, Jan Philippé, Ine Moors
The natural history of primary eosinophilia remains highly variable and is characterized by underlying disease heterogeneity. Chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) is a rare and aggressive disease characterized by non-specific cytogenetic abnormalities or elevated blasts, with high risk of transformation to acute leukemia. We describe a case of CEL-NOS with two hierarchically related non-specific cytogenetic rearrangements, associated with an NPM1 mutation and followed by evolution to secondary AML...
2018: Leukemia Research Reports
https://www.readbyqxmd.com/read/29890129/microrna-199a-b-5p-enhance-imatinib-efficacy-via-repressing-wnt2-signaling-mediated-protective-autophagy-in-imatinib-resistant-chronic-myeloid-leukemia-cells
#13
Peng-Hsu Chen, Ann-Jeng Liu, Kuo-Hao Ho, Ya-Ting Chiu, Zhe-Harn Anne Lin, Yi-Ting Lee, Chwen-Ming Shih, Ku-Chung Chen
Imatinib (IM) is a first-line therapeutic drug for chronic myeloid leukemia (CML), a hematological disease. Mutations in the BCR-ABL domain increase formation of IM resistance in CML. However, not all patients are BCR-ABL domain-mutant dependent. Investigating non-mutant mechanisms in the development of acquired IM resistance is a critical issue. We explored the mechanisms which influence IM efficacy and resistance in CML. Higher protective autophagy was identified in IM-resistant K562 (K562R) cells. Inhibition of autophagy by the inhibitors, chloroquine and 3-methyladenine, enhanced IM's efficacy in K562R cells...
June 8, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29883054/genetic-compensation-of-runx-family-transcription-factors-in-leukemia
#14
REVIEW
Yasuhiko Kamikubo
RUNX1 is a transcription factor belonging to the Core Binding Factor (CBF) family. It is considered to be a master regulator of hematopoiesis and has been regarded as a tumor suppressor because it is essential for definitive hematopoiesis in vertebrates. It is one of the most frequent target genes of chromosomal translocation in leukemia, and germ line mutation of RUNX1 causes familial platelet disorder with associated myeloid malignancies (FPDMM). Somatic cell mutations and chromosomal abnormalities, including those of RUNX1, are observed in myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelomonocytic leukemia (CMML) at a high frequency...
June 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29878489/chronic-myelomonocytic-leukemia-2018-update-on-diagnosis-risk-stratification-and-management
#15
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (∼15%-20% over 3-5 years). DIAGNOSIS: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 109 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼ 30% of patients, while >90% have gene mutations...
June 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29878287/molecular-monitoring-of-tunisian-patients-with-chronic-myeloid-leukemia
#16
Samia Menif, Yosra Ben Youssef, Hatem Bellaaj, Raihane Ben Lakhal, Adnen Laatiri
BACKGROUND: bcr-abl fusion gene is the hallmark of chronic myeloid leukemia (CML). RQ-PCR provides an accurate measure of the total leukemia cell mass and the degree to which bcr-abl transcripts are reduced by therapy correlates with progression free survival. AIM: We report molecular assessment of residual disease in CML Tunisian patients. METHODS: Between June 2003 and December 2014 we measured bcr-abl mRNA levels in peripheral blood from all Tunisian patients by quantitative real time polymerase chain reaction (RQ-PCR)...
December 2017: La Tunisie Médicale
https://www.readbyqxmd.com/read/29877248/-splicing-factor-mutations-in-myelodysplastic-syndromes
#17
Yusuke Shiozawa
Splicing factor mutations represent a novel class of driver mutations in myelodysplastic syndromes, where four genes, including SF3B1, SRSF2, U2AF1, and ZRSR2, are most frequently affected. SF3B1 and SRSF2 mutations show prominent specificity to the syndrome subtypes characterized by increased ring sideroblasts and chronic myelomonocytic leukemia, respectively. These mutations are suspected to be involved in the pathogenesis of the above mentioned syndromes most likely via abnormal RNA splicing. However, the precise mechanism and target genes have not been fully understood...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29875417/setbp1-induces-transcription-of-a-network-of-development-genes-by-acting-as-an-epigenetic-hub
#18
Rocco Piazza, Vera Magistroni, Sara Redaelli, Mario Mauri, Luca Massimino, Alessandro Sessa, Marco Peronaci, Maciej Lalowski, Rabah Soliymani, Caterina Mezzatesta, Alessandra Pirola, Federica Banfi, Alicia Rubio, Delphine Rea, Fabio Stagno, Emilio Usala, Bruno Martino, Leonardo Campiotti, Michele Merli, Francesco Passamonti, Francesco Onida, Alessandro Morotti, Francesca Pavesi, Marco Bregni, Vania Broccoli, Marc Baumann, Carlo Gambacorti-Passerini
SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel-Giedion syndrome. Here we show that SETBP1 binds to gDNA in AT-rich promoter regions, causing activation of gene expression through recruitment of a HCF1/KMT2A/PHF8 epigenetic complex. Deletion of two AT-hooks abrogates the binding of SETBP1 to gDNA and impairs target gene upregulation. Genes controlled by SETBP1 such as MECOM are significantly upregulated in leukemias containing SETBP1 mutations...
June 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29874990/a-chemical-approach-to-overcome-tyrosine-kinase-inhibitors-resistance-learning-from-chronic-myeloid-leukemia
#19
Enrico Zanforlin, Giuseppe Zagotto, Giovanni Ribaudo
BACKGROUND: The possibilities of treatment for oncological diseases are growing enormously in the last decades. Unfortunately, these developments have led to the onset of resistances with regards to the new treatments. This is particularly true if we face with the therapeutic field of Tyrosine Kinase Inhibitors (TKIs). This review gives an overview of possible TKI resistances that can occur during the treatment of an oncologic diesease and available strategies that can be adopted, taking cues from a successful example such as CML Methods: We performed a literature search for peer-reviewed articles using different databases, such as PubMed and Scopus, and exploiting different keywords and different logical operators...
June 6, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29872884/myeloid-neoplasms-with-t-16-21-q24-q22-runx1-runx1t3-mimics-acute-myeloid-leukemia-with-runx1-runx1t1
#20
Huifei Liu, Sa A Wang, Ellen J Schlette, Jie Xu, Jeffrey L Jorgensen, C Cameron Yin, Shaoying Li, L Jeffrey Medeiros, Guilin Tang
Chromosome translocation t(16;21)(q24;q22)/RUNX1-RUNX1T3 is an infrequent but recurrent chromosomal abnormality identified in myeloid neoplasms, with only 25 cases have been reported to date. Here, we report eight cases (six women and two men) of myeloid neoplasms associated with t(16;21)(q24;q22): five with therapy-related myeloid neoplasms, two with relapsed acute myeloid leukemia (AML), and one with blast phase of chronic myeloid leukemia. Morphologic and immunophenotypic features include granulocytic dysplasia, blasts with prominent perinuclear hof, large orange-pink granules, long and slim Auer rods, and aberrant expression of CD19...
June 5, 2018: Annals of Hematology
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