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Chronic myeloid leukaemia

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https://www.readbyqxmd.com/read/28636094/characterization-of-clonal-philadelphia-negative-cytogenetic-abnormalities-in-a-large-cohort-of-chronic-myeloid-leukemia
#1
Xiangjun Chen, Jine Zheng, Kaiwei Liang, Yanli He, Wen Du, Juan Li, Wei Liu, Yanjie Hu, Junxia Yao
OBJECTIVES: Clonal Philadelphia-negative Cytogenetic Abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enrolled. METHODS: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31...
June 21, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28615140/imaging-features-of-myeloproliferative-neoplasms
#2
REVIEW
I G Murphy, E L Mitchell, L Raso-Barnett, A L Godfrey, E M Godfrey
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of haematological disorders including polycythaemia vera (PV), essential thrombocythaemia (ET), primary myelofibrosis (PMF), and chronic myeloid leukaemia (CML). These disorders show large overlap in genetic and clinical presentations, and can have many different imaging manifestations. Unusual thromboses, embolic events throughout the systemic or pulmonary vasculature, or osseous findings can often be clues to the underlying disease. There is limited literature about the imaging features of these disorders, and this may result in under-diagnosis...
June 11, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28599500/notable-roles-of-ezh2-and-dnmt1-in-epigenetic-dormancy-of-the-shp1-gene-during-the-progression-of-chronic-myeloid-leukaemia
#3
Jing Wang, Luoming Hua, Ming Guo, Lin Yang, Xiaojun Liu, Yanmeng Li, Xiaoyan Shang, Jianmin Luo
Tumor development is associated with the methylation of cytosine-guanine (CpG) islands. The occurrence of methylation requires several factors, such as DNA methylation systems and polycomb group (PcG) proteins. At present, novel drugs are needed for the treatment of chronic myeloid leukaemia (CML), particularly considering the current prognosis of CML. The methylation status of the Src homology 2 domain-containing tyrosine phosphatase 1 (SHP1) gene, a negative regulator of signal transduction, has been identified as being altered in numerous haematological malignancies...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28588176/evaluation-of-bcr-abl-gene-rearrangement-among-bangladeshi-chronic-myeloid-leukaemia-patients
#4
T F Dipta, A Datta, A Tarif, M A Mottalib, A M Yunus, M A Muttalib, S Choudhury, M A Islam
Chronic Myeloid Leukaemia (CML) is a clonal myeloproloferative disorder. Presence of molecular translocation t (9; 22) in CML patients can be confirmed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Among haematological malignancies CML is the commonest leukaemia of adults in Asia. Despite this, there are very few studies published from Bangladesh, documenting the frequency of bcr-abl fusion transcripts. So, we would like to perform this observational study to evaluate bcr-abl fusion transcripts and demographic status among RT-PCR positive chronic phase CML patients at BIRDEM & other two centers of Dhaka city, Bangladesh where patients admitted from different districts of Bangladesh in the period of January 2010 to June 2012...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28587395/effectiveness-of-imatinib-mesylate-over-etoposide-in-the-treatment-of-sensitive-and-resistant-chronic-myeloid-leukaemia-cells-in-vitro
#5
Roslina Husaini, Munirah Ahmad, Zubaidah Zakaria
Chronic myeloid leukaemia (CML) is a form of leukaemia derived from the myeloid cell lineage. Imatinib mesylate, the breakpoint cluster region-abelson murine leukeamia kinase inhibitor, is a specific reagent used in the clinical treatment of CML. The DNA topoisomerase II inhibitor, etoposide, is also employed as a therapeutic, though it is used to a lesser extent. The present study aims to evaluate the effects of CML-targeted therapy, utilising imatinib mesylate and etoposide in the in vitro treatment of parental sensitive and adriamycin-resistant CML in the K562 and K562/ADM cell lines, respectively...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28586310/effective-control-of-acute-myeloid-leukaemia-and-acute-lymphoblastic-leukaemia-progression-by-telomerase-specific-adoptive-t-cell-therapy
#6
Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T Scupoli, Michael I Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte, Stefano Ugel
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566209/de-escalation-of-tyrosine-kinase-inhibitor-dose-in-patients-with-chronic-myeloid-leukaemia-with-stable-major-molecular-response-destiny-an-interim-analysis-of-a-non-randomised-phase-2-trial
#7
Richard E Clark, Fotios Polydoros, Jane F Apperley, Dragana Milojkovic, Christopher Pocock, Graeme Smith, Jenny L Byrne, Hugues de Lavallade, Stephen G O'Brien, Tony Coffey, Letizia Foroni, Mhairi Copland
BACKGROUND: Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia with deep molecular responses; however, patients with stable major molecular response (MMR), but not MR4, have not been studied, nor has the effect of treatment de-escalation rather than outright cessation. We aimed to examine the effects of treatment de-escalation as a prelude to complete cessation, not only in patients with MR4 or greater, but also in those with MMR but not MR4...
May 26, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28557248/ponatinib-induced-widespread-ichthyosiform-eruption
#8
F Derlino, S Barruscotti, P Zappasodi, V Brazzelli, C Vassallo
Ponatinib is a new potent third-generation tyrosine kinase inhibitor (TKI), developed for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukaemia (ALL) resistant to first (imatinib) and second generation (dasatinib and nilotinib) TK-inhibitors. Aimed at wild type and mutant BCR-ABL, ponatinib demonstrates significant anti-leukemic activity and holds much promise in treating other malignancies, including gastrointestinal stromal tumors (GIST)(1;2). This article is protected by copyright...
May 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28522574/single-cell-immune-profiling-by-mass-cytometry-of-newly-diagnosed-chronic-phase-chronic-myeloid-leukaemia-treated-with-nilotinib
#9
Stein-Erik Gullaksen, Jørn Skavland, Sonia Gavasso, Vinko Tosevski, Krzysztof Warzocha, Claudia Dumrese, Augustin Ferrant, Tobias Gedde-Dahl, Andrzej Hellmann, Jeroen Janssen, Boris Labar, Alois Lang, Waleed Majeed, Georgi Mihaylov, Jesper Stentoft, Leif Stenke, Josef Thaler, Noortje Thielen, Gregor Verhoef, Jaroslava Voglova, Gert Ossenkoppele, Andreas Hochhaus, Henrik Hjorth-Hansen, Satu Mustjoki, Sieghart Sopper, Francis Giles, Kimmo Porkka, Dominik Wolf, Bjørn Tore Gjertsen
Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognostication, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukaemia. Changes in phosphorylated Bcr-Abl1 and its involved signalling pathways were readily identifiable in peripheral blood single cells already within 3 hours of per oral nilotinib dosing...
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28514443/cancer-progression-by-reprogrammed-bcaa-metabolism-in-myeloid-leukaemia
#10
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/28480959/research-on-the-epigenetic-regulation-mechanism-of-the-ptpn6-gene-in-advanced-chronic-myeloid-leukaemia
#11
Xiaokun Zhang, Lin Yang, Xiaojun Liu, Ziyuan Nie, Xingzhe Wang, Yuxia Pan, Jianmin Luo
PTPN6, a tyrosine phosphatase protein, plays a negative role in cell signal transduction and is negatively correlated with tumour formation and growth. However, epigenetic regulation mechanism of the PTPN6 gene in advanced chronic myeloid leukaemia (CML) remains unclear. This study investigated bone marrow or blood samples from 44 CML patients and 10 healthy volunteers. KCL22 and K562 cells were cultured and treated with demethylation drugs and histone deacetylase inhibitors. Real time quantitative polymerase chain reaction (qPCR), methylation-specific PCR, bisulfite sequencing PCR, Western blotting, co-immunoprecipitation and chromatin immunoprecipitation (ChIP) was performed...
May 8, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28467002/the-use-of-imatinib-resistance-mutation-analysis-to-direct-therapy-in-philadelphia-chromosome-bcr-abl1-positive-chronic-myeloid-leukaemia-patients-failing-imatinib-treatment-in-patan-hospital-nepal
#12
REVIEW
Gyan K Kayastha, Nora Ranjitkar, Radha Gurung, Raj Kumar Kc, Sanjit Karki, Roshan Shrestha, Piyush Rajbhandari, Raj K Thapa, Buddhi Poudyal, Paras Acharya, David J Roberts, Bruce Hayes, Mark Zimmerman, Buddha Basnyat
Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28452111/epigenetic-dysregulation-of-id4-predicts-disease-progression-and-treatment-outcome-in-myeloid-malignancies
#13
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/28449207/targeting-anti-apoptotic-bcl2-family-proteins-in-haematological-malignancies-from-pathogenesis-to-treatment
#14
REVIEW
Meike Vogler, Harriet S Walter, Martin J S Dyer
The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti-apoptotic functions of BCL2 proteins using structure-based design to produce specific inhibitors of protein-protein interactions has been achieved for BCL2, MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3-mimetics...
April 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28444623/treatment-adherence-in-chronic-myeloid-leukaemia-patients-receiving-tyrosine-kinase-inhibitors
#15
Anna Rychter, Piotr Jerzmanowski, Adam Hołub, Zofia Specht-Szwoch, Violetta Kalinowska, Urszula Tęgowska, Ilona Seferyńska, Agnieszka Kołkowska-Leśniak, Ewa Lech-Marańda, Joanna Góra-Tybor
Failure to comply with treatment recommendations is very common in patients, but still poorly recognised by doctors. The current practice of using oral therapy on a large scale has been increasingly adopted for cancer patients. Chronic myeloid leukaemia (CML) is just such an example, where the introduction of taking new oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now revolutionised the treatment. The aim of our study was to assess treatment adherence in a group of Polish CML patients (a survey was conducted on 140 patient aged ≥18 years) treated with oral TKI (imatinib, dasatinib and nilotinib) taking into account the following variables: gender, age, education, place of residence, family circumstances and duration of therapy...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28384883/dasatinib-induced-cardiac-tamponade-a-rare-association
#16
Sushant Wattal, Mugula Sudhakar Rao, Gs Naveen Chandra, U K Abdul Razak, K Ranjan Shetty
Drug induced cardiac tamponade is rare. Therapy for imatinib resistant Chronic Myeloid Leukaemia (CML) is an emerging challenge in clinical haematology. For such cases treatment with second line tyrosine kinase inhibitors like dasatinib has resulted in improved outcomes. Dasatinib is a second line BCR-ABL tyrosine kinase inhibitor used in the treatment of Imatinib resistant or Imatinib intolerant CML. Dasatinib has been reported to cause severe pericardial effusions in 1% of all patients in clinical studies...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28374668/morphometric-and-densitometric-analysis-of-heterochromatin-during-cell-differentiation-using-the-leukaemic-granulocytic-lineage-as-a-convenient-model
#17
K Smetana, D Mikulenková, H Klamová
Granulocytic early progenitors and terminally differentiated - mature granulocytes with segmented nuclei were studied using computer-assisted diameter and heterochromatin optical image densitometry to provide more information on the nuclear size and heterochromatin condensation state. Bone marrow smears of patients suffering from chronic myeloid leukaemia untreated as well as treated with "specific" anti-leukaemic therapy with imatinib mesylate are a convenient model for such study because they possess a satisfactory number of cells for diameter and optical density measurements...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28369812/treating-philadelphia-chromosome-bcr-abl1-positive-patients-with-glivec-imatinib-mesylate-10%C3%A2-years-experience-at-patan-hospital-nepal
#18
Gyan K Kayastha, Nora Ranjitkar, Radha Gurung, Raj K Kc, Sanjit Karki, Roshan Shrestha, Raj K Thapa, Piyush Rajbhandari, Buddhi Poudyal, Paras Acharya, David J Roberts, Bruce Hayes, Mark Zimmerman, Buddha Basnyat, Aaron Mansfield
The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28369779/allogeneic-stem-cell-transplantation-in-patients-with-atypical-chronic-myeloid-leukaemia-a-retrospective-study-from-the-chronic-malignancies-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#19
Francesco Onida, Liesbeth C de Wreede, Anja van Biezen, Diderik-Jan Eikema, Jenny L Byrne, Anna P Iori, Rik Schots, Alexandra Jungova, Johannes Schetelig, Jürgen Finke, Hendrik Veelken, Jan-Erik Johansson, Charles Craddock, Matthias Stelljes, Matthias Theobald, Ernst Holler, Urs Schanz, Nicolaas Schaap, Jörg Bittenbring, Eduardo Olavarria, Yves Chalandon, Nicolaus Kröger
Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%...
June 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28365527/imatinib-discontinuation-in-chronic-myeloid-leukaemia-patients-with-undetectable-bcr-abl-transcript-level-a%C3%A2-systematic-review-and-a-meta-analysis
#20
REVIEW
Leonardo Campiotti, Matteo Basilio Suter, Luigina Guasti, Rocco Piazza, Carlo Gambacorti-Passerini, Anna Maria Grandi, Alessandro Squizzato
PURPOSE: Tyrosine kinase inhibitors (TKIs) are the cornerstones of treatment for patients with chronic myeloid leukaemia (CML). In recent years, several studies were conducted to evaluate the safety of TKIs discontinuation. We performed a systematic review of the literature to determine the incidence of CML relapse, to identify possible factors relapse rates and to evaluate the long-term safety in CML patients with stable undetectable BCR-ABL transcript level who discontinued TKIs. DESIGN: Studies evaluating TKIs discontinuation in CML patients with undetectable BCR-ABL transcript level were identified by electronic search of MEDLINE and EMBASE database until May 2015...
March 30, 2017: European Journal of Cancer
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