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Acute myeloid leukemia

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https://www.readbyqxmd.com/read/28110409/body-mass-index-is-a-prognostic-factor-in-adult-patients-with-acute-myeloid-leukemia
#1
Taiki Ando, Etsuko Yamazaki, Eriko Ogusa, Yoshimi Ishii, Wataru Yamamoto, Kenji Motohashi, Takayoshi Tachibana, Maki Hagihara, Kenji Matsumoto, Masatsugu Tanaka, Chizuko Hashimoto, Hideyuki Koharazawa, Katsumichi Fujimaki, Jun Taguchi, Hiroyuki Fujita, Heiwa Kanamori, Shin Fujisawa, Hideaki Nakajima
Body mass index (BMI), which represents the proportion of weight to height, is a controversial prognostic factor for acute myeloid leukemia (AML). We evaluated prognostic value of BMI in Japanese AML. The study included 369 adult patients with newly diagnosed AML who were administered either daunorubicin or idarubicin with cytarabine as induction chemotherapy. The patients were categorized into two groups according to their BMI: the NW group (BMI < 25.0 kg/m(2); normal and underweight) and OW group (BMI ≥ 25...
January 21, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28110381/minimal-residual-disease-in-acute-myeloid-leukemia
#2
REVIEW
Pamela J Sung, Selina M Luger
New technology and improved understanding of the pathogenesis of acute leukemias have allowed for sensitive detection of minimal residual disease (MRD). Despite many years of research demonstrating the prognostic value of MRD, there is no standard of care for measurement of MRD in acute myeloid leukemia. The techniques for assessment are continuing to improve at a rapid pace; however, the benefit of risk-adapted approaches for MRD positive disease remains a major question. This review focuses on recent methodological advances for MRD detection, the role of MRD in prognostication, and current application of the available evidence in guiding therapy decisions...
January 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28110245/bipartite-network-analysis-reveals-metabolic-gene-expression-profiles-that-are-highly-associated-with-the-clinical-outcomes-of-acute-myeloid-leukemia
#3
Fanfan Xie, Mingxiong He, Li He, Keqin Liu, Menglong Li, Guoquan Hu, Zhining Wen
Dysregulated and reprogrammed metabolism are one of the most important characteristics of cancer, and exploiting cancer cell metabolism can aid in understanding the diverse clinical outcomes for patients. To investigate the differences in metabolic pathways among patients with acute myeloid leukemia (AML) and differential survival outcomes, we systematically conducted microarray data analysis of the metabolic gene expression profiles from 384 patients available from the Gene Expression Omnibus and Cancer Genome Atlas databases...
January 6, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28109402/frontline-treatment-of-acute-myeloid-leukemia-in-adults
#4
REVIEW
Gevorg Tamamyan, Tapan Kadia, Farhad Ravandi, Gautam Borthakur, Jorge Cortes, Elias Jabbour, Naval Daver, Maro Ohanian, Hagop Kantarjian, Marina Konopleva
Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients' age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40-50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30 to 40% up to 80 to 90%...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28108543/disease-characteristics-and-prognostic-implications-of-cell-surface-flt3-receptor-cd135-expression-in-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#5
Katherine Tarlock, Todd A Alonzo, Michael R Loken, Robert B Gerbing, Rhonda E Ries, Richard Aplenc, Lillian Sung, Susana Raimondi, Betsy A Hirsch, Samir B Kahwash, Amy McKenney, E Anders Kolb, Alan S Gamis, Soheil Meshinchi
PURPOSE: The FLT3 cell-surface receptor tyrosine kinase (CD135) is expressed in a majority of both acute lymphoid leukemia (ALL) and myeloid leukemia (AML). However, the prognostic significance of CD135 expression in AML remains unclear. We therefore evaluated the association between FLT3 surface expression and disease characteristics and outcomes in pediatric patients with AML. EXPERIMENTAL DESIGN: We analyzed FLT3 receptor expression on AML blasts by multi-dimensional flow cytometry and its association with disease characteristics, clinical outcomes, and FLT3 transcript level in 367 children with AML treated on the Children's Oncology Group trial AAML0531...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108507/flt3-and-jak2-mutations-in-acute-myeloid-leukemia-promote-inter-chromosomal-homologous-recombination-and-the-potential-for-copy-neutral-loss-of-heterozygosity-cn-loh
#6
Terry J Gaymes, Azim Mohamedali, Anthony Eiliazadeh, David Darling, Ghulam J Mufti
Acquired copy neutral loss-of-heterozygosity (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here we show that constitutive signaling driven by mutated FLT3 and JAK2 confers inter-chromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared to wild type FLT3 NK-AML...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108472/relapsed-acute-promyelocytic-leukemia-lacks-classic-leukemic-promyelocyte-morphology-and-can-create-diagnostic-challenges
#7
Vanessa J Dayton, Robert W McKenna, Sophia L Yohe, Michelle M Dolan, Elizabeth Courville, Harold Alvarez, Michael A Linden
OBJECTIVES: Although current therapies for acute promyelocytic leukemia (APL), such as all-trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. METHODS: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review...
January 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28108471/prognostic-significance-of-residual-acute-myeloid-leukemia-in-bone-marrow-samples-taken-prior-to-allogeneic-hematopoietic-cell-transplantation
#8
Alexandra E Kovach, Andrew M Brunner, Amir T Fathi, Yi-Bin Chen, Robert P Hasserjian
OBJECTIVES: We sought to identify features in routine evaluation of pre-hematopoietic cell transplantation (HCT) bone marrow samples from patients with acute myeloid leukemia (AML) that influenced patient outcome. METHODS: Of 140 patients, evidence of residual leukemia (RL) was identified in 38 (27%) of pre-HCT samples, as defined by 5% or more aspirate blasts, increased blood blasts, clustered or necrotic blasts on biopsy specimens, and/or leukemia-associated karyotypic abnormalities...
January 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28108287/antitumor-activity-of-a-novel-and-orally-available-inhibitor-of-serine-palmitoyltransferase
#9
Masahiro Yaguchi, Sachio Shibata, Yoshinori Satomi, Megumi Hirayama, Ryutaro Adachi, Yasutomi Asano, Takuto Kojima, Yasuhiro Hirata, Akio Mizutani, Atsushi Kiba, Yoji Sagiya
Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28108271/comparative-effectiveness-of-busulfan-and-fludarabine-versus-fludarabine-and-400-cgy-total-body-irradiation-conditioning-regimens-for-aml-mds
#10
Moaath Mustafa Ali, Donna M Abounader, Lisa A Rybicki, Melissa A Yurch, Jamie Starn, Christina Ferraro, Victoria Winslow, Betty K Hamilton, Aaron T Gerds, Hien Liu, Robert Dean, Brian T Hill, Brad Pohlman, Steven Andresen, Rabi Hanna, Matt Kalaycio, Brian J Bolwell, Navneet S Majhail, Ronald Sobecks
Allogeneic hematopoietic cell transplantation (alloHCT) conditioning regimen intensity has varied for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 had FluTBI. The BuFlu group received more red blood cell transfusions (P=0.02) and had a longer time to platelet recovery (P=0...
January 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#11
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28106537/down-regulation-of-pseudogene-vimentin-2p-is-associated-with-poor-outcome-in-de-novo-acute-myeloid-leukemia
#12
Ling-Ling Zhai, Jiao Zhou, Jing Zhang, Xi Tang, Ling-Yu Zhou, Jia-Yu Yin, Minse-Evola Deniz Vanessa, Wen Peng, Jiang Lin, Zhao-Qun Deng
OBJECTIVES: This study was intended to investigate the expression status of Vimentin 2p (VIM 2p), a pseudogene of Vimentin, and further analyze its clinical significance in AML patients. METHODS: Real-time quantitative PCR (RQ-PCR) was employed to explore the expression status of VIM 2p in 128 patients with de novo AML and 36 healthy controls. RESULTS: The expression level of VIM 2p was significantly decreased compared with healthy controls (P< 0...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106288/nuclear-inositide-signaling-via-phospholipase-c
#13
Stefano Ratti, Sara Mongiorgi, Giulia Ramazzotti, Matilde Y Follo, Giulia A Mariani, Pann-Ghill Suh, James A McCubrey, Lucio Cocco, Lucia Manzoli
The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases. In this prospect we analyze the role of PI-PLCβ1 nuclear isoform in relation to the cell cycle regulation, the cell differentiation and different physiopathological pathways focusing on the importance of the nuclear localization from both molecular and clinical point of view. PI-PLCβ1 is essential for G1/S transition through DAG and Cyclin D3 and plays also a central role in G2/M progression through Cyclin B1 and PKCα...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28104648/identification-of-merkel-cell-polyomavirus-from-a-patient-with-acute-myeloid-leukemia
#14
Y Song, P Gyarmati
Merkel cell polyomavirus (MCPyV) is an oncogenic virus associated with Merkel cell carcinoma, an aggressive form of skin cancer with a high (>30%) mortality rate. The virus has a high incidence in patients with immunosuppressed conditions, such as AIDS or leukemia, or following organ transplantation. Here, we report the complete genomic sequence of MCPyV identified from a blood sample from a patient with acute myeloid leukemia.
January 19, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28103640/addition-of-cladribine-to-the-standard-induction-treatment-improves-outcomes-in-a-subset-of-elderly-aml-patients-results-of-a-randomized-polish-adult-leukemia-group-palg-phase-ii-trial
#15
Agnieszka Pluta, Tadeusz Robak, Agata Wrzesien-Kus, Bozena Katarzyna Budziszewska, Kazimierz Sulek, Ewa Wawrzyniak, Magdalena Czemerska, Malgorzata Zwolinska, Aleksandra Golos, Aleksandra Holowiecka-Goral, Slawomira Kyrcz-Krzemien, Jaroslaw Piszcz, Janusz Kloczko, Monika Mordak-Domagala, Andrzej Lange, Małgorzata Razny, Krzysztof Madry, Wieslaw Wiktor-Jedrzejczak, Sebastian Grosicki, Aleksandra Butrym, Kazimierz Kuliczkowski, Krzysztof Warzocha, Jerzy Holowiecki, Sebastian Giebel, Richard Szydlo, Agnieszka Wierzbowska
Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients, the present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age...
January 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28103300/expression-profiling-of-ribosome-biogenesis-factors-reveals-nucleolin-as-a-novel-potential-marker-to-predict-outcome-in-aml-patients
#16
Virginie Marcel, Frédéric Catez, Caroline M Berger, Emeline Perrial, Adriana Plesa, Xavier Thomas, Eve Mattei, Sandrine Hayette, Pierre Saintigny, Philippe Bouvet, Jean-Jacques Diaz, Charles Dumontet
Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28100265/allogeneic-stem-cell-transplantation-in-adult-patients-with-acute-myeloid-leukaemia-and-17p-abnormalities-in-first-complete-remission-a-study-from-the-acute-leukemia-working-party-alwp-of-the-european-society-for-blood-and-marrow-transplantation-ebmt
#17
Xavier Poiré, Myriam Labopin, Johan Maertens, Ibrahim Yakoub-Agha, Didier Blaise, Norbert Ifrah, Gérard Socié, Tobias Gedde-Dhal, Nicolaas Schaap, Jan J Cornelissen, Stéphane Vigouroux, Jaime Sanz, Lucienne Michaux, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. METHODS: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. RESULTS: One hundred thirty-nine patients with confirmed abn(17p) have been selected...
January 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28099273/making-the-most-of-hypomethylating-agents-in-myelodysplastic-syndrome
#18
Geetika Bhatt, William Blum
PURPOSE OF REVIEW: Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year. RECENT FINDINGS: Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with reformulated HMA that have more favorable pharmacokinetics (including oral bioavailability)...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099272/mixed-phenotype-acute-leukemia-current-challenges-in-diagnosis-and-therapy
#19
Ofir Wolach, Richard M Stone
PURPOSE OF REVIEW: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. RECENT FINDINGS: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors...
January 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28099271/innovative-strategies-for-adverse-karyotype-acute-myeloid-leukemia
#20
Sabine Blum, Gabriele Greve, Michael Lübbert
PURPOSE OF REVIEW: Adverse karyotype acute myeloid leukemia is a disease particularly of older patients, but also observed in younger patients. Despite all efforts, standard chemotherapy is still generally applied in fit patients, as already for decades, and for nearly all different subtypes of acute myeloid leukemia. Lack of more specifically targeted therapy and the often older age of the patients are complicating treatment, and in the subgroup of patients achieving a complete remission, the strikingly high frequency of relapse is a characteristic of this disease...
January 17, 2017: Current Opinion in Hematology
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