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https://www.readbyqxmd.com/read/29784935/a-causal-mechanism-for-childhood-acute-lymphoblastic-leukaemia
#1
REVIEW
Mel Greaves
In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6)-runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia...
May 21, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29784869/childhood-leukaemia-may-be-preventable-by-exposure-to-infections-in-early-life
#2
Nigel Hawkes
No abstract text is available yet for this article.
May 21, 2018: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29784646/latest-developments-in-muc1-immunotherapy
#3
REVIEW
Joyce Taylor-Papadimitriou, Joy M Burchell, Rosalind Graham, Richard Beatson
Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29784137/factors-influencing-the-documentation-of-fertility-related-discussions-for-adolescents-and-young-adults-with-cancer
#4
G Skaczkowski, V White, K Thompson, H Bibby, M Coory, R Pinkerton, W Nicholls, L M Orme, R Conyers, M B Phillips, M Osborn, R Harrup, A Anazodo
PURPOSE: A cancer diagnosis and treatment may have significant implications for a young patient's future fertility. Documentation of fertility-related discussions and actions is crucial to providing the best follow-up care, which may occur for many years post-treatment. This study examined the rate of medical record documentation of fertility-related discussions and fertility preservation (FP) procedures for adolescents and young adults (AYAs) with cancer in Australia. METHODS: A retrospective review of medical records for 941 patients in all six Australian states...
June 2018: European Journal of Oncology Nursing: the Official Journal of European Oncology Nursing Society
https://www.readbyqxmd.com/read/29780592/preleukemic-and-second-hit-mutational-events-in-an-acute-myeloid-leukemia-patient-with-a-novel-germline-runx1-mutation
#5
Isaac Ks Ng, Joanne Lee, Christopher Ng, Bustamin Kosmo, Lily Chiu, Elaine Seah, Michelle Meng Huang Mok, Karen Tan, Motomi Osato, Wee-Joo Chng, Benedict Yan, Lip Kun Tan
Background: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29778661/epigenetic-dysregulation-of-zeb1-is-involved-in-lmo2-promoted-t-cell-acute-lymphoblastic-leukaemia-leukaemogenesis
#6
Chao Wu, Jianjun Li, Chenchen Tian, Wen Shi, Huimin Jiang, Zhen Zhang, Hang Wang, Quansheng Zhang, Wei Sun, Peiqing Sun, Rong Xiang, Shuang Yang
T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777163/evolution-of-cll-treatment-from-chemoimmunotherapy-to-targeted-and-individualized-therapy
#7
REVIEW
Jan A Burger, Susan O'Brien
During the past 5 years, a number of highly active novel agents, including kinase inhibitors targeting BTK or PI3Kδ, an antagonist of the antiapoptotic protein BCL-2, and new anti-CD20 monoclonal antibodies, have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). In these exciting times, care is needed to optimally integrate these novel agents into the traditional treatment algorithm without overlooking or compromising the benefits of established treatments, especially chemoimmunotherapy...
May 18, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29776374/the-toxoplasma-gondii-me-49-strain-upregulates-levels-of-a20-that-inhibit-nf-%C3%AE%C2%BAb-activation-and-promotes-apoptosis-in-human-leukaemia-t-cell-lines
#8
Qian Chen, Min-Hui Pang, Xiao-Hong Ye, Guang Yang, Chen Lin
BACKGROUND: Acute T-lymphocyte leukaemia is a form of haematological malignancy with abnormal activation of NF-κB pathway, which results in high expression of A20 and ABIN1, which constitute a negative feedback mechanism for the regulation of NF-κB activation. Clinical studies have found that acute T-lymphocyte leukaemia patients are susceptible to Toxoplasma gondii infection; however, the effect of T. gondii on the proliferation and apoptosis of human leukaemia T-cells remains unclear...
May 18, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29767839/jak2-v617f-positive-acute-myeloid-leukaemia-aml-a-comparison-between-de-novo-aml-and-secondary-aml-transformed-from-an-underlying-myeloproliferative-neoplasm-a-study-from-the-bone-marrow-pathology-group
#9
Jason Aynardi, Rashmi Manur, Paul R Hess, Seble Chekol, Jennifer J D Morrissette, Daria Babushok, Elizabeth Hexner, Heesun J Rogers, Eric D Hsi, Elizabeth Margolskee, Attilio Orazi, Robert Hasserjian, Adam Bagg
The JAK2 V617F mutation is characteristic of most Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and occurs rarely in de novo acute myeloid leukaemia (AML). We sought to characterize AMLs that harbour this mutation and distinguish those that arise de novo (AML-DN) from those that reflect transformation of an underlying MPN (AML-MPN). Forty-five patients with JAK2 V617F-mutated AML were identified; 15 were AML-DN and 30 were AML-MPN. AML-MPN cases were more likely to have splenomegaly (P = 0·02), MPN-like megakaryocytes and higher mean JAK2 V617F VAF at diagnosis (P = 0·04)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767474/mesenchymal-stromal-cells-from-shwachman-diamond-syndrome-patients-fail-to-recreate-a-bone-marrow-niche-in-vivo-and-exhibit-impaired-angiogenesis
#10
Donatella Bardelli, Erica Dander, Cristina Bugarin, Claudia Cappuzzello, Alice Pievani, Grazia Fazio, Paolo Pierani, Paola Corti, Piero Farruggia, Carlo Dufour, Simone Cesaro, Marco Cipolli, Andrea Biondi, Giovanna D'Amico
Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767433/t-6-9-p23-q34-1-acute-myeloid-leukaemia-with-cup-like-blasts
#11
Claire Bories, Thomas Boyer
No abstract text is available yet for this article.
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767427/azacitidine-in-the-real-world-an-evaluation-of-1101-higher-risk-myelodysplastic-syndrome-low-blast-count-acute-myeloid-leukaemia-patients-in-ontario-canada
#12
Lee Mozessohn, Matthew C Cheung, Saber Fallahpour, Tripat Gill, Asmaa Maloul, Liying Zhang, Olivia Lau, Rena Buckstein
The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767411/mek1-2-inhibition-by-binimetinib-is-effective-as-a-single-agent-and-potentiates-the-actions-of-venetoclax-and-abt-737-under-conditions-that-mimic-the-chronic-lymphocytic-leukaemia-cll-tumour-microenvironment
#13
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767410/combination-targeted-therapy-in-chronic-lymphocytic-leukaemia-can-pre-clinical-studies-translate-to-the-clinic
#14
EDITORIAL
Nikolaos Ioannou, Alan G Ramsay
No abstract text is available yet for this article.
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765597/cancer-cell-transmission-via-the-placenta
#15
REVIEW
Mel Greaves, William Hughes
Cancer cells have a parasitic propensity in the primary host but their capacity to transit between individuals is severely restrained by two factors: a lack of a route for viable cell transfer and immune recognition in allogeneic, secondary recipients. Several examples of transmissible animal cancers are now recognised. In humans, the only natural route for transmission is via the haemochorial placenta which is permissive for cell traffic. There are three special examples of this occurring in utero : maternal to foetus, intraplacental twin to twin leukaemias and choriocarcinoma-extra-embryonic cells to mother...
2018: Evolution, Medicine, and Public Health
https://www.readbyqxmd.com/read/29765150/phase-i-studies-of-azd1208-a-proviral-integration-moloney-virus-kinase-inhibitor-in-solid-and-haematological-cancers
#16
Jorge Cortes, Kenji Tamura, Daniel J DeAngelo, Johann de Bono, David Lorente, Mark Minden, Geoffrey L Uy, Hagop Kantarjian, Lisa S Chen, Varsha Gandhi, Robert Godin, Karen Keating, Kristen McEachern, Karthick Vishwanathan, Janet Elizabeth Pease, Emma Dean
BACKGROUND: Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours. METHODS: Two dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours...
May 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29764519/plasmodium-yoelii-infection-inhibits-murine-leukaemia-wehi-3-cell-proliferation-in-vivo-by-promoting-immune-responses
#17
Zhen-Zhen Tong, Zheng-Ming Fang, Qi Zhang, Yun Zhan, Yue Zhang, Wan-Fang Jiang, Xiao Hou, Yong-Long Li, Ting Wang
BACKGROUND: Leukaemia is a malignant leukocyte disorder with a high fatality rate, and current treatments for this disease are unsatisfactory. Therefore, new therapeutic strategies for leukaemia must be developed. Malaria parasite infection has been shown to be effective at combating certain neoplasms in animal experiments. This study is to demonstrate the anti-leukaemia activity of malaria parasite Plasmodium yoelii (P. yoelii) infection,. METHODS: In this study, the proportion of CD3, CD19, CD11b and Mac-3 cells was analysed by flow cytometry; the levels of IFN-γ and TNF-α in individual serum samples were measured by enzyme-linked immunosorbent assay, and the phagocytic activity of macrophages and natural killer (NK) cell activity were measured by flow cytometry...
May 16, 2018: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/29761849/muc1-c-drives-myeloid-leukaemogenesis-and-resistance-to-treatment-by-a-survivin-mediated-mechanism
#18
Dina Stroopinsky, Hasan Rajabi, Myrna Nahas, Jacalyn Rosenblatt, Maryam Rahimian, Athalia Pyzer, Ashujit Tagde, Akriti Kharbanda, Salvia Jain, Turner Kufe, Rebecca K Leaf, Eleni Anastasiadou, Michal Bar-Natan, Shira Orr, Maxwell D Coll, Kristen Palmer, Adam Ephraim, Leandra Cole, Abigail Washington, Donald Kufe, David Avigan
Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with an unmet need for improved therapies. Responses to standard cytotoxic therapy in AML are often transient because of the emergence of chemotherapy-resistant disease. The MUC1-C oncoprotein governs critical pathways of tumorigenesis, including self-renewal and survival, and is aberrantly expressed in AML blasts and leukaemia stem cells (LSCs). However, a role for MUC1-C in linking leukaemogenesis and resistance to treatment has not been described...
May 15, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29759551/genomics-and-pharmacogenomics-of-pediatric-acute-lymphoblastic-leukemia
#19
REVIEW
Chuan Wu, Wei Li
Acute lymphoblastic leukaemia (ALL) is a prevalent form of pediatric cancer that accounts for 70-80% of all leukemias. Genome-based analysis, exome sequencing, transcriptomics and proteomics have provided insight into genetic classification of ALL and helped identify novel subtypes of the disease. B and T cell-based ALL are two well-characterized genomic subtypes, significantly marked by bone marrow disorders, along with mutations in trisomy 21 and T53. The other ALLs include Early T-cell precursor ALL, Philadelphia chromosome-like ALL, Down syndrome-associated ALL and Relapsed ALL...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29755704/breastfeeding-in-patients-with-chronic-myeloid-leukaemia-case-series-with-measurements-of-drug-concentrations-in-maternal-milk-and-literature-review
#20
Ekaterina Chelysheva, Sergey Aleshin, Evgenia Polushkina, Roman Shmakov, Igor Shokhin, Ghermes Chilov, Anna Turkina
Breastfeeding in patients with chronic myeloid leukaemia (CML) during tyrosine kinase inhibitors (TKIs) therapy is not recommended but interruption of TKI treatment may cause the loss of remission. We studied the 3 cases of pregnancy and breastfeeding in women with CML and observed that stopping treatment without major molecular response may end in haematological relapse. The concentrations of nilotinib and imatinib in maternal milk were measured and nilotinib distribution in human breast milk was demonstrated for the first time...
2018: Mediterranean Journal of Hematology and Infectious Diseases
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