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https://www.readbyqxmd.com/read/29151174/the-impact-of-remission-status-on-patients-experiences-with-acute-myeloid-leukemia-aml-an-exploratory-analysis-of-longitudinal-patient-reported-outcomes-data
#1
Neha Kayastha, Steven P Wolf, Susan C Locke, Gregory P Samsa, Areej El-Jawahri, Thomas W LeBlanc
PURPOSE: Shared decision-making in acute myeloid leukemia (AML) requires understanding patients' longitudinal experiences of illness, but little is known about the impact of remission status on patient-reported outcomes (PROs). We aimed to explore the association between remission status and PROs 6-12 months following induction chemotherapy. METHODS: Forty-two patients completed three validated instruments characterizing symptom burden (Patient Care Monitor v2...
November 18, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29151133/treatment-of-relapsed-aml-and-mds-after-allogeneic-stem-cell-transplantation-with-decitabine-and-dli-a-retrospective-multicenter-analysis-on-behalf-of-the-german-cooperative-transplant-study-group
#2
Thomas Schroeder, Christina Rautenberg, William Krüger, Uwe Platzbecker, Gesine Bug, Juliane Steinmann, Stefan Klein, Olaf Hopfer, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe
In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11)...
November 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29150948/methylation-associated-dok1-and-dok2-down-regulation-potential-biomarkers-for-predicting-adverse-prognosis-in-acute-myeloid-leukemia
#3
Pin-Fang He, Zi-Jun Xu, Jing-Dong Zhou, Xi-Xi Li, Wei Zhang, De-Hong Wu, Zhi-Hui Zhang, Xin-Yue Lian, Xin-Yu Yao, Zhao-Qun Deng, Jiang Lin, Jun Qian
DOK-1 and DOK-2 (DOK1/2) are closely related members of downstream of tyrosine kinase (DOK) family genes, which are found to be frequently rearranged in several hematopoietic cancers. However, the clinical implications of DOK1/2 in acute myeloid leukemia (AML) remain largely unknown. To investigate the clinical significance, real-time quantitative PCR (RQ-PCR) was carried out to detect DOK1/2 expressions in 125 de novo AML patients and 28 healthy controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were applied to detect DOK1/2 methylation level and density...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150453/high-bcat1-expression-mimics-idh-mutations-in-acute-myeloid-leukemia
#4
(no author information available yet)
High BCAT1 expression is linked to shorter survival in patients with IDH- and TET2-wild-type AML.
November 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29150117/molecular-genetic-techniques-for-gains-and-losses-of-genomic-material-in-a-case-of-acute-myeloid-leukemia
#5
Mauren Fernanda Moller Dos Santos, Camila Clozato Lara, Elvira Deolinda Rodrigues Pereira Velloso
No abstract text is available yet for this article.
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29150116/acute-myeloid-leukemia-with-e1a2-bcr-abl1-fusion-gene-two-cases-with-peculiar-molecular-and-clinical-presentations
#6
Fernanda Borges da Silva, João Agostinho Machado-Neto, Luisa Corrêa de Araujo Koury, Virginia Helena Leira Lipoli Bertini, Cristina Alonso Ratis, Maria de Lourdes Lopes Ferrari Chauffaille, Elvira Deolinda Rodrigues Pereira Velloso, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabiola Traina
No abstract text is available yet for this article.
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29149610/first-approved-kinase-inhibitor-for-aml
#7
John E J Rasko, Timothy P Hughes
Activating mutations of FLT3 occur in about 30% of acute myeloid leukemia (AML) cases and are associated with relapse and poor prognosis. Midostaurin is the first drug approved for AML since 2000, and the first multi-kinase inhibitor approved for the FLT3-mutant subtype. To view this Bench to Bedside, open or download the PDF.
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29149401/introduction-how-we-encountered-tctp-and-our-purpose-in-studying-it
#8
Adam Telerman, Robert Amson
In this brief introduction, we describe our encounter with TCTP. Back in 2000, we discovered TCTP in two quite different ways: first, we looked at protein partners of TSAP6 and one of them was TCTP. Then, in collaboration with Sidney Brenner, we performed a high-throughput differential screening comparing the parental cancer cells with revertants. The results indicated that TCTP was of the most differentially expressed genes. These two approaches were carried out only months apart. They guided our research and led to the discoveries of drugs that inhibit the function of TCTP...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149122/leukostasis-management-to-prevent-crisis-in-acute-leukemia%C3%A2
#9
Lisa M Blackburn, Shelly Brown, Aimee Munyon, Michelle Orovets
BACKGROUND: Hyperleukocytosis, a peripheral white blood cell count greater than 100,000/mm3,is most commonly seen in patients with newly diagnosed or relapsed acute lymphoblastic leukemia and acute myeloid leukemia. Leukostasis is a reduction in blood flow related to hyperviscosity. Hyperleukocytosis, causing leukostasis, is an oncologic emergency and requires an exacting assessment and rapid response with appropriate intervention to prevent morbidity and mortality in the first week after diagnosis...
December 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29148089/impact-of-gene-mutations-on-treatment-response-and-prognosis-of-acute-myeloid-leukemia-secondary-to-myeloproliferative-neoplasms
#10
G Venton, F Courtier, A Charbonnier, E D'Incan, C Saillard, B Mohty, M J Mozziconacci, D Birnbaum, A Murati, N Vey, J Rey
Acute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prognostic markers and efficient treatments. We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics, the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS)...
November 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#11
Judith M Hönes, Aniththa Thivakaran, Lacramioara Botezatu, Pradeep Patnana, Symone Vitoriano da Conceição Castro, Yahya S Al-Matary, Judith Schütte, Karen B I Fischer, Lothar Vassen, André Görgens, Ulrich Dührsen, Bernd Giebel, Cyrus Khandanpour
The differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reduced GFI1 gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#12
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146910/an-unexpected-protein-interaction-promotes-drug-resistance-in-leukemia
#13
Aaron Pitre, Yubin Ge, Wenwei Lin, Yao Wang, Yu Fukuda, Jamshid Temirov, Aaron H Phillips, Jennifer L Peters, Yiping Fan, Jing Ma, Amanda Nourse, Chandrima Sinha, Hai Lin, Richard Kriwacki, James R Downing, Tanja A Gruber, Victoria E Centonze, Anjaparavanda P Naren, Taosheng Chen, John D Schuetz
The overall survival of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related therapeutic targets remains a major goal for this disease. Here we show that expression of MPP1, a PDZ-domain-containing protein, highly correlated with ABCC4 in AML, is associated with worse overall survival in AML. Murine hematopoietic progenitor cells overexpressing MPP1 acquired the ability to serially replate in methylcellulose culture, a property crucially dependent upon ABCC4. The highly conserved PDZ-binding motif of ABCC4 is required for ABCC4 and MPP1 to form a protein complex, which increased ABCC4 membrane localization and retention, to enhance drug resistance...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146707/outcomes-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-myeloid-leukemia-harboring-t-7-11-p15-p15
#14
Kaito Harada, Noriko Doki, Jun Aoki, Jinichi Mori, Shinichiro Machida, Masayoshi Masuko, Naoyuki Uchida, Yuho Najima, Takahiro Fukuda, Heiwa Kanamori, Hiroyasu Ogawa, Shuichi Ota, Kazuei Ogawa, Satoshi Takahashi, Masanobu Kasai, Akio Maeda, Koji Nagafuji, Toshiro Kawakita, Tatsuo Ichinohe, Yoshiko Atsuta
No abstract text is available yet for this article.
November 16, 2017: Haematologica
https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#15
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#16
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144072/relapse-and-cytogenetic-evolution-in-myeloid-neoplasms
#17
Natalie Ertz-Archambault, Katalin Kelemen
Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms...
December 2017: Panminerva Medica
https://www.readbyqxmd.com/read/29143813/ship1-but-not-an-aml-derived-ship1-mutant-suppresses-myeloid-leukemia-growth-in-a-xenotransplantation-mouse-model
#18
M Täger, S Horn, E Latuske, P Ehm, M Schaks, M Nalaskowski, B Fehse, W Fiedler, C Stocking, J Wellbrock, M Jücker
Constitutive activation of the PI3K/AKT signaling pathway is found in ~50-70% of AML patients. The SH2-containing inositol 5-phosphatase 1 (SHIP1) is a negative regulator of PI3K/AKT signaling in hematopoietic cells. SHIP1 knockout mice develop a myeloproliferative syndrome and concomitant deletion of SHIP1 and the tumor suppressor PTEN leads to the development of lethal B-cell lymphomas. In the study presented here, we investigated the role of SHIP1 as a tumor suppressor in myeloid leukemia cells in an in vivo xenograft transplantation model...
November 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29143282/hypomethylating-agents-for-treatment-and-prevention-of-relapse-after-allogeneic-blood-stem-cell-transplantation
#19
REVIEW
Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe
Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29142466/higher-pd-1-expression-concurrent-with-exhausted-cd8-t-cells-in-patients-with-de-novo-acute-myeloid-leukemia
#20
Jiaxiong Tan, Shaohua Chen, Yuhong Lu, Danlin Yao, Ling Xu, Yikai Zhang, Lijian Yang, Jie Chen, Jing Lai, Zhi Yu, Kanger Zhu, Yangqiu Li
Objective: To investigate the association between the T cell inhibitory receptor programmed death 1 (PD-1) and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia (AML) and AML in complete remission (CR). Methods: Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+, CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed, untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
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