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acute leukaemia

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https://www.readbyqxmd.com/read/29342136/clonal-evolution-mechanisms-in-nt5c2-mutant-relapsed-acute-lymphoblastic-leukaemia
#1
Gannie Tzoneva, Chelsea L Dieck, Koichi Oshima, Alberto Ambesi-Impiombato, Marta Sánchez-Martín, Chioma J Madubata, Hossein Khiabanian, Jiangyan Yu, Esme Waanders, Ilaria Iacobucci, Maria Luisa Sulis, Motohiro Kato, Katsuyoshi Koh, Maddalena Paganin, Giuseppe Basso, Julie M Gastier-Foster, Mignon L Loh, Renate Kirschner-Schwabe, Charles G Mullighan, Raul Rabadan, Adolfo A Ferrando
Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342133/a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#2
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a 'super-enhancer' is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29340063/a-molecular-signature-of-dormancy-in-cd34-cd38-acute-myeloid-leukaemia-cells
#3
Mazin Gh Al-Asadi, Grace Brindle, Marcos Castellanos, Sean T May, Ken I Mills, Nigel H Russell, Claire H Seedhouse, Monica Pallis
Dormant leukaemia initiating cells in the bone marrow niche are a crucial therapeutic target for total eradication of acute myeloid leukaemia. To study this cellular subset we created and validated an in vitro model employing the cell line TF-1a, treated with Transforming Growth Factor β1 (TGFβ1) and a mammalian target of rapamycin inhibitor. The treated cells showed decreases in total RNA, Ki-67 and CD71, increased aldehyde dehydrogenase activity, forkhead box 03A (FOX03A) nuclear translocation and growth inhibition, with no evidence of apoptosis or differentiation...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339097/safety-and-preliminary-efficacy-of-venetoclax-with-decitabine-or-azacitidine-in-elderly-patients-with-previously-untreated-acute-myeloid-leukaemia-a-non-randomised-open-label-phase-1b-study
#4
Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study...
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29339096/a-new-option-for-remission-induction-in-acute-myeloid-leukaemia
#5
Carsten Müller-Tidow, Richard F Schlenk
No abstract text is available yet for this article.
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29338345/effect-of-anacardium-occidentale-leaf-extract-on-human-acute-lymphoblastic-leukaemia-cell-lines
#6
Janaína M Santos, Nathalia M Cury, José A Yunes, Jorge A López, Maria L Hernández-Macedo
Anacardium occidentale leaves are used in folk medicine due its therapeutic properties attributed to phenolic compounds. Therefore, this study was undertaken on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE interfered in the cell cycle progression, inducing apoptosis by activation of casp3 at lower concentrations, thence, a promising candidate for the development of new cancer drugs.
January 16, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29337707/induction-chemotherapy-in-acute-myeloid-leukaemia-origins-and-emerging-directions
#7
Vivek A Upadhyay, Amir T Fathi
PURPOSE OF REVIEW: This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. RECENT FINDINGS: We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations...
January 13, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29337382/frailty-in-patients-with-acute-myeloid-leukaemia-conceptual-misapprehension-of-chronological-age
#8
E G Umit, M Baysal, A M Demir
In haematology practice, patients with acute myeloid leukaemia (AML) are generally assessed for frailty only if they are older and not able to tolerate intensive and remission targeted treatments. We aimed to focus on frailty in patients with AML, in all ages and aimed to evaluate its role and practicality in daily routine. Data of patients diagnosed and treated for AML between 2006 and 2016 are recorded and assessed for their survival predictivity. One hundred and ninety-seven patients were <65 years of age and 175 were ≥65...
January 16, 2018: European Journal of Cancer Care
https://www.readbyqxmd.com/read/29336301/-acute-promyelocytic-leukaemia
#9
Michael Tøstesen, Lene S G Østergård, Eigil Kjeldsen, Jesper Stentoft, Jan M Nørgaard
Acute promyelocytic leukaemia has changed from being a highly fatal to a highly curable disease. Over time, key discoveries have identified the genetic and molecular abnormalities, which cause the disease. First choice of treatment has now changed from all-trans retinoic acid (ATRA) and chemotherapy to a chemo-free combination of arsenic trixoide and ATRA. This new regimen has shown equal responses and overall cure rates compared with the previous standard of care containing conventional chemotherapy, but with much lower toxicity...
January 15, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29336300/-successful-treatment-of-acute-promyelocytic-leukaemia-without-chemotherapy-and-blood-transfusion
#10
Michael Tøstesen, Lene S G Østgård, Eigil Kjeldsen, Jesper Stentoft, Jan M Nørgaard
Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year-old female patient, who due to religious conviction refused supportive therapy with blood products. A treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was successful without the use of blood transfusions...
January 15, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29333125/association-between-slc19a1-gene-polymorphism-and-high-dose-methotrexate-toxicity-in-childhood-acute-lymphoblastic-leukaemia-and-non-hodgkin-malignant-lymphoma-introducing-a-haplotype-based-approach
#11
Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona, Vita Dolzan
Background: We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods: Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results: Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29330269/central-nervous-system-graft-versus-host-disease-cns-gvhd-after-allogeneic-haematopoietic-stem-cell-transplantation
#12
Karolina Polchlopek Blasiak, Federico Simonetta, Maria-Isabel Vargas, Yves Chalandon
A 60-year-old man presented with impaired consciousness and psychomotor agitation after a second allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor for acute myeloid leukaemia. Clinical, biological and radiological evidence suggested a diagnosis of central nervous system graft-versus-host disease (CNS-GvHD). After intrathecal infusion of methylprednisolone, the clinical symptoms as well as the radiological abnormalities disappeared. The present report illustrates the difficulties in the diagnosis and the management of CNS-GvHD, a very rare and still challenging neurological complication that can occur after allogeneic HSCT...
January 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29327808/the-rocky-road-to-personalized-medicine-in-acute-myeloid-leukaemia
#13
REVIEW
Bryan Brinda, Irum Khan, Brian Parkin, Heiko Konig
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29326122/growth-factor-independence-1b-a-key-player-in-the-genesis-and-maintenance-of-acute-myeloid-leukaemia-and-myelodysplastic-syndrome
#14
Aniththa Thivakaran, Lacramiora Botezatu, Judith M Hönes, Judith Schütte, Lothar Vassen, Yahya S Al-Matary, Pradeep Patnana, Amos Zeller, Michael Heuser, Felicitas Thol, Razif Gabdoulline, Nadine Olberding, Daria Frank, Marina Suslo, Renata Köster, Klaus Lennartz, Andre Görgens, Bernd Giebel, Bertram Opalka, Ulrich Dührsen, Cyrus Khandanpour
Differentiation of haematopoietic stem cells is regulated by a concert of different transcription factors. Disturbed transcription factors function can be the basis of (pre)malignancies such as myelodysplastic syndrome or acute myeloid leukaemia. Growth factor independence 1b is a repressing transcription factor regulating quiescence of hematopoietic stem cellss and differentiation of erythrocytes and platelets. Here, we show that low expression of Growth factor independence 1b in blast cells is associated with an inferior prognosis of myelodysplastic syndrome and acute myeloid leukaemia patients...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29322418/analysis-of-histone-modifications-in-acute-myeloid-leukaemia-using-chromatin-immunoprecipitation
#15
Benjamin J Shields, Andrew Keniry, Marnie E Blewitt, Matthew P McCormack
Chromatin Immunoprecipitation (ChIP) using antibodies specific for histone modifications is a powerful technique for assessing the epigenetic states of cell populations by either quantitative PCR (ChIP-PCR) or next generation sequencing analysis (ChIP-Seq). Here we describe the procedure for ChIP of histone marks in myeloid leukaemia cell lines and the subsequent purification of genomic DNA associated with repressive and activating histone modifications for further analysis. This procedure can be widely applied to a variety of histone marks to assess both activating and repressive modifications in the context of myeloid leukaemia...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321348/influence-of-thiopurine-methyltransferase-gene-polymorphism-on-egyptian-children-with-acute-lymphoblastic-leukaemia
#16
Azza A G Tantawy, Fatma S E Ebeid, Amira A M Adly, Eman El-Ghoroury, Mai Mostafa
Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29318591/immune-checkpoint-molecules-in-acute-myeloid-leukaemia-managing-the-double-edged-sword
#17
REVIEW
Willemijn Hobo, Tim J A Hutten, Nicolaas P M Schaap, Harry Dolstra
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29318584/treatment-of-relapsed-refractory-acute-myeloid-leukaemia-in-adults
#18
REVIEW
Armin Rashidi, Daniel J Weisdorf, Nelli Bejanyan
The prognosis of relapsed acute myeloid leukaemia (AML) is poor and treatment is challenging. While the most potent treatment modality for patients who achieve a complete remission after relapse is still allogeneic haematopoietic cell transplantation (allo-HCT), both transplant-related mortality and relapse rates are high and many patients are not candidates for this approach. After a few decades of relative stasis in this field, a large number of novel approaches have become available to tackle this highly fatal disease...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29314523/pneumocystis-jirovecii-pneumonia-in-patients-with-acute-myeloid-leukaemia
#19
Hung Chang, Ming-Chung Kuo, Tung-Liang Lin, Jin-Hou Wu, Po-Nan Wang
The association of Pneumocystis jirovecii pneumonia (PJP) and acute myeloid leukaemia (AML) is not clearly defined. In our experience of 291 patients with AML, 20 (14 males and 6 females, median age 56) developed PJP (incidence 6.8%). Thirteen patients (65%) survived until discharge from hospital. We conclude that PJP is not uncommon among patients with AML. In clinical care of AML, awareness of PJP should be heightened and prophylaxis should be considered.
January 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29311715/the-bone-marrow-niche-in-mds-and-mgus-implications-for-aml-and-mm
#20
REVIEW
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
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