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Acute myeloid leukemia

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https://www.readbyqxmd.com/read/28828639/therapeutic-decision-making-in-elderly-patients-with-acute-myeloid-leukemia-conventional-intensive-chemotherapy-versus-hypomethylating-agent-therapy
#1
Sang-Bo Oh, Sung-Woo Park, Joo-Seop Chung, Won-Sik Lee, Ho-Seop Lee, Su-Hee Cho, Yoon-Suk Choi, Sung-Nam Lim, Ho-Jin Shin
Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70...
August 21, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28828165/angiogenesis-status-in-patients-with-acute-myeloid-leukemia-from-diagnosis-to-post-hematopoietic-stem-cell-transplantation
#2
REVIEW
M Mohammadi Najafabadi, K Shamsasenjan, P Akbarzadehalaleh
As already proven in solid tumors, increased angiogenesis leads to increased number of blood vessels, resulting in unfavorable outcomes and resistance to chemotherapy. It was previously thought that angiogenesis plays no role in the pathogenesis of acute myeloid leukemia (AML), due to the fact that AML is a liquid tumor. However, many studies have suggested that increased angiogenesis has important roles in patients with AML, including increased numbers of vessels in bone marrow and pro-angiogenic factors, as well as decreased anti-angiogenic factors...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28827408/hematopoietic-stem-cell-involvement-in-bcr-abl1-positive-all-as-potential-mechanism-of-resistance-to-blinatumomab-therapy
#3
Inga Nagel, Marius Bartels, Johannes Duell, Hans-Heinrich Oberg, Sandra Ussat, Henrike Bruckmueller, Oliver Ottmann, Heike Pfeifer, Heiko Trautmann, Nicola Gökbuget, Almuth Caliebe, Dieter Kabelitz, Michael Kneba, Heinz-August Horst, Dieter Hoelzer, Max S Topp, Ingolf Cascorbi, Reiner Siebert, Monika Brüggemann
The bispecific T-cell engager blinatumomab targeting CD19 can induce complete remission in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, some patients ultimately relapse with loss of CD19-antigen on leukemic cells which has been established as a novel escape mechanism to CD19-specific immunotherapies. Here, we provide evidence that CD19-negative relapse after CD19-directed therapy in BCP-ALL may be due to selection of preexisting CD19-negative malignant progenitor cells...
August 21, 2017: Blood
https://www.readbyqxmd.com/read/28822593/decreased-expression-of-microrna-122-is-associated-with-an-unfavorable-prognosis-in-childhood-acute-myeloid-leukemia-and-function-analysis-indicates-a-therapeutic-potential
#4
Juan Yang, Yufang Yuan, Xiaochun Yang, Ze Hong, Lijuan Yang
MicroRNA (miR)-122 functions as a tumor suppressor in various human cancers. However, its involvement in childhood acute myeloid leukemia (AML) remains unknown. In this study, quantitative real-time PCR assay demonstrated that miR-122 expression in bone marrow specimens from AML children were significantly lower than that in non-malignant controls (P<0.001). Statistically, AML children with low miR-122 expression more frequently had large white blood cell count (P=0.022), French-American-British classification subtype M7 (P<0...
June 28, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28821995/expression-of-the-pol-gene-of-human-endogenous-retroviruses-herv-k-and-w-in-leukemia-patients
#5
Massimiliano Bergallo, Paola Montanari, Katia Mareschi, Chiara Merlino, Massimo Berger, Ilaria Bini, Valentina Daprà, Ilaria Galliano, Franca Fagioli
The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression...
August 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28819408/opposite-effects-of-set7-9-on-apoptosis-of-human-acute-myeloid-leukemia-cells-and-lung-cancer-cells
#6
Ye Gu, Yuan Wang, Xinling Wang, Lili Gao, Weiping Yu, Wei-Feng Dong
SET7/9 is a protein lysine methyltransferases (PLMTs or PKMTs) which methylates both histone H3K4 and non-histone proteins including transcriptional factors, tumor suppressors, and membrane-associated receptors. Methylation of these proteins alters protein activity and leads to changes in cellular behavior and a series of biological processes. This study aims to investigate the role of SET7/9 in human acute myeloid leukemia (AML) and non-small-cell lung cancer (NSCLC). We examined the expression of SET7/9 in AML cells and NSCLC cells and detected the methylation status of the SET7/9 promoter region...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819278/interleukin-4-induces-apoptosis-of-acute-myeloid-leukemia-cells-in-a-stat6-dependent-manner
#7
P Peña-Martínez, M Eriksson, R Ramakrishnan, M Chapellier, C Högberg, C Orsmark-Pietras, J Richter, A Andersson, T Fioretos, M Järås
Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Consistent with these findings, we found that IL4 stimulation of AML cells induced Stat6 phosphorylation and that disruption of Stat6 using CRISPR/Cas9-genetic engineering rendered cells partially resistant to IL4-induced apoptosis...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28818952/enasidenib-approved-for-aml-but-best-uses-unclear
#8
(no author information available yet)
The FDA approved the targeted therapy enasidenib for patients with refractory or relapsed acute myeloid leukemia with mutant IDH2 The drug produces remissions in some patients and may reduce the need for blood transfusions, although researchers acknowledge that the FDA's approval came with less supporting evidence than usual.
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28816795/voriconazole-antifungal-prophylaxis-in-children-with-malignancies-a-nationwide-study
#9
Zoi Dorothea Pana, Maria Kourti, Katerina Vikelouda, Antonia Vlahou, Nikolaos Katzilakis, Maria Papageorgiou, Dimitrios Doganis, Loizos Petrikkos, Anna Paisiou, Dimitrios Koliouskas, Antonios Kattamis, Eftichia Stiakaki, Maria Chatzistilianou, Helen Vasilatou-Kosmidis, Sophia Polychronopoulou, Stelios Grafakos, Emmanuel Roilides
BACKGROUND: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients' demographics, outcome, and adverse event (AE) data were recorded. RESULTS: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28816792/development-of-secondary-acute-myeloid-leukemia-in-a-pediatric-patient-concurrently-receiving-primary-therapy-for-ewing-sarcoma
#10
Brandon R McNew, Benjamin W Darbro, Deqin Ma, David J Gordon
Ewing sarcoma is a pediatric bone and soft tissue sarcoma that requires intensive therapy, which can cause secondary malignancies. We present a rare case of early, treatment-related AML in a pediatric patient concurrently receiving primary therapy for Ewing sarcoma. Despite AML-directed therapy, our patient died secondary to complications of hyperleukocytosis. Cytogenetic and mutation profiling of the leukemia cells revealed the DNA-topoisomerase-II-inhibitor-associated t(9;11)(p22;q23) translocation and clonal KRAS and BRAF mutations...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28816238/acute-myeloid-leukemia-transforms-the-bone-marrow-niche-into-a-leukemia-permissive-microenvironment-through-exosome-secretion
#11
B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto, A S Stein, V A Pullarkat, S K Hui, N Carlesso, Y-H Kuo, R Bhatia, G Marcucci, C-C Chen
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia-growth-permissive and normal-hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Pre-conditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth...
August 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#12
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814670/mtg16-is-a-tumor-suppressor-in-colitis-associated-carcinoma
#13
Elizabeth M McDonough, Caitlyn W Barrett, Bobak Parang, Mukul K Mittal, J Joshua Smith, Amber M Bradley, Yash A Choksi, Lori A Coburn, Sarah P Short, Joshua J Thompson, Baolin Zhang, Shenika V Poindexter, Melissa A Fischer, Xi Chen, Jiang Li, Frank L Revetta, Rishi Naik, M Kay Washington, Michael J Rosen, Scott W Hiebert, Keith T Wilson, Christopher S Williams
MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16-/- mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814193/sirolimus-and-mirabegron-interaction-in-a-hematopoietic-cell-transplant-patient
#14
Jeff A Engle, Christina Fair
Purpose Hematopoietic cell transplant patients are exposed to numerous classes of medications. Transplant practitioners must vigilantly monitor for drug interactions especially involving immunosuppressants. We report a hematopoietic cell transplant patient receiving sirolimus who developed supratherapeutic serum concentrations after initiating mirabegron. Summary A 31-year-old, 98 kg female received a second umbilical cord blood transplant four years after the first transplant for relapsed acute myeloid leukemia...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#15
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Giorgina Specchia, Francesco Albano
The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and "bridge-to-transplant" settings...
August 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#16
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28812970/indole-3-carbinol-induces-g1-cell-cycle-arrest-and-apoptosis-through-aryl-hydrocarbon-receptor-in-thp-1-monocytic-cell-line
#17
Saeed Mohammadi, Fakhri Sadat Seyedhosseini, Nasser Behnampour, Yaghoub Yazdani
OBJECTIVES: The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. METHODS: MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28812528/acute-leukemia-in-horses
#18
Carina J Cooper, Stefan M Keller, Luis G Arroyo, Joanne Hewson, Daniel Kenney, Dorothee Bienzle
Leukemia is broadly divided into acute and chronic lymphocytic and myeloid types based on the proportion of blasts, morphology of cells, and expression of specific antigens on neoplastic cells. Classifying leukemia in horses can be challenging if blasts predominate and since few antibodies to identify cell types are available. The objective of this study was to describe in detail the clinical and pathologic features of acute leukemia in horses. Twelve horses ranging from 0.2 to 25.9 years of age were diagnosed with acute leukemia...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28812191/improved-outcome-of-childhood-acute-myeloid-leukemia-in-an-eastern-european-country-lithuanian-experience
#19
Igne Kairiene, Ramune Pasauliene, Nadezda Lipunova, Goda Vaitkeviciene, Lina Rageliene, Jelena Rascon
The reported treatment outcomes of children treated for cancer in Eastern European countries are inferior to those in Northern/Western Europe. We hypothesized that recent survival rates could be comparable to the current standards and performed a population-based analysis of treatment outcome of childhood acute myeloid leukemia (AML) in Lithuania, a small Eastern European country. Children < 18 years old who were treated for AML from 2000 to 2013 were included (n = 54). Estimates of 5-year event-free (EFS5y) and overall survival (OS5y) rates were analyzed...
August 15, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28811942/spontaneous-complete-remission-in-a-patient-with-acute-myeloid-leukemia-and-severe-sepsis
#20
Rambod Mozafari, Mahsa Moeinian, Ali Asadollahi-Amin
Without treatment, acute myeloid leukemia (AML) is almost always fatal. Spontaneous remission of AML is a rare phenomenon and usually with a short duration. The exact mechanisms are unknown. However, its association with infection and blood transfusions has been described. We report a 53-year-old male who presented with severe sepsis and who was diagnosed with AML (M4). He has experienced complete spontaneous remission with relatively long duration. To the best of our knowledge, it is the first case of spontaneous remission described in Iran...
2017: Case Reports in Hematology
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