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Myelodysplastic syndrom

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https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#1
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910027/recurrent-cytogenetic-abnormalities-in-acute-myeloid-leukemia
#2
John J Yang, Tae Sung Park, Thomas S K Wan
The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910026/recurrent-cytogenetic-abnormalities-in-myelodysplastic-syndromes
#3
Meaghan Wall
Cytogenetic analysis has an essential role in diagnosis, classification, and prognosis of myelodysplastic syndromes (MDS). Some cytogenetic abnormalities are sufficiently characteristic of MDS to be considered MDS defining in the appropriate clinical context. MDS with isolated del(5q) is the only molecularly defined MDS subtype. The genes responsible for many aspects of 5q- syndrome, the distinct clinical phenotype associated with this condition, have now been identified. Cytogenetics forms the cornerstone of the most widely adopted prognostic scoring systems in MDS, the international prognostic scoring system (IPSS) and the revised international prognostic scoring system (IPPS-R)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27906673/multiplex-ligation-dependent-probe-amplification-assay-identifies-additional-copy-number-changes-compared-with-r-band-karyotype-and-provide-more-accuracy-prognostic-information-in-myelodysplastic-syndromes
#4
Jingya Wang, Xiaofei Ai, Tiejun Qin, Zefeng Xu, Yue Zhang, Jinqin Liu, Bing Li, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Shiqiang Qu, Wenyu Cai, Kun Ru, Yujiao Jia, Gang Huang, Zhijian Xiao
Cytogenetic analysis provides important diagnostic and prognostic information for patients with Myelodysplastic syndromes (MDS) and plays an essential role in the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R). Multiplex ligation-dependent probe amplification (MLPA) assay is a recently developed technique to identify targeted cytogenetic aberrations in MDS patients. In the present study, we evaluated the results obtained using an MLPA assay in 437 patients with MDS to determine the efficacy of MLPA analysis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905102/elevated-fetal-haemoglobin-is-a-predictor-of-better-outcome-in%C3%A2-mds-aml-patients-receiving-5-aza-2-deoxycytidine-decitabine
#5
Michael Lübbert, Gabriele Ihorst, Philipp N Sander, Ljudmila Bogatyreva, Heiko Becker, Pierre W Wijermans, Stefan Suciu, Emmanuel Bissé, Rainer Claus
Although azanucleoside DNA-hypomethylating agents (HMAs) are routinely used for the treatment of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), very few outcome predictors have been established. Expression of the β-like globin gene locus is tightly regulated by DNA methylation, is HMA-sensitive in vitro, and fetal haemoglobin (HbF) expression is under study as a potential biomarker for response of MDS patients to azacitidine. We determined HbF expression in 16 MDS and 36 AML patients receiving decitabine (DAC)...
December 1, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27902785/apoptosis-related-gene-expression-profiling-in-hematopoietic-cell-fractions-of-mds-patients
#6
Saskia Mc Langemeijer, Niccolo Mariani, Ruth Knops, Christian Gilissen, Rob Woestenenk, Theo de Witte, Gerwin Huls, Bert A van der Reijden, Joop H Jansen
Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells...
2016: PloS One
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#7
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899806/preleukemia-one-name-many-meanings
#8
REVIEW
H P Koeffler, G Leong
Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia which nearly always progress to AML. More recently investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations which were also present at diagnosis of AML...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899359/how-i-treat-atypical-chronic-myeloid-leukemia
#9
Jason Gotlib
Atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML) is a rare myelodysplastic syndrome/myeloproliferative neoplasm for which no current standard of care exists. The challenges of atypical CML relate to its heterogeneous clinical and genetic features, high rate of transformation to acute myeloid leukemia, and historically poor survival. Therefore, allogeneic hematopoietic stem cell transplantation should always be an initial consideration for eligible patients with a suitable donor. Non-transplant approaches for treating aCML have otherwise largely relied on adopting treatment strategies used for MDS and MPN...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#10
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27898660/asthma-and-risk-of-myelodysplastic-syndromes-a-population-based-cohort-study
#11
Henrik Frederiksen, Dóra Körmendiné Farkas, Erzsébet Horváth-Puhó, Jan M Nørgaard, Mette Nørgaard, Henrik T Sørensen
BACKGROUND: Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS. METHODS: We undertook this nationwide population-based cohort study on patients with a first-time hospital-based asthma diagnosis during 2002-2013 and followed them for the development of MDS/chronic myelomonocytic leukaemia (CMML). RESULTS: We identified 75 995 patients with incident asthma and no previous MDS/CMML diagnosis...
November 29, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27897450/vascular-endothelial-growth-factor-overexpression-in-myelodysplastic-syndrome-bone-marrow-cells-biological-and-clinical-implications
#12
Rosangela Invernizzi, Erica Travaglino, Matteo Giovanni Della Porta, Luca Malcovati, Anna Gallì, Raffaella Bastia, Mariella Ciola, Ilaria Ambaglio, Emanuela Boveri, Vittorio Rosti, Mario Cazzola
In myelodysplastic syndrome (MDS), vascular endothelial growth factor (VEGF) may have regulatory effects on the hematopoietic system and contribute to disease progression. We analyzed by immunocytochemistry VEGF expression in bone marrow (BM) cells from 188 patients with MDS and 96 non-hemopathic subjects. We also measured VEGF BM plasma levels and in vitro VEGF release. Our aims were to evaluate whether VEGF expression abnormalities were associated with relevant laboratory or clinical findings and their possible prognostic value...
November 29, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27895446/a-case-of-fatal-sepsis-due-to-multidrug-resistant-corynebacterium-striatum
#13
M Chatzopoulou, T Koufakis, I Voulgaridi, I Gabranis, M Tsiakalou
BACKGROUND: Although non-diphtheria corynebacteria have traditionally been regarded as avirulent members of human bacterial flora, their pathogenic potential is increasingly recognized in our time. Reasons for this include the prolonged survival of severely ill and immunocompromised patients, the development of more invasive diagnostic and therapeutic procedures and the sub-optimal use of antibiotics that disrupts normal microbial balance and favors superinfections. CASE REPORT: We present a rare case of sepsis due to multidrug-resistant Corynebacterium striatum in a 76-year-old host...
January 2016: Hippokratia
https://www.readbyqxmd.com/read/27894982/multiple-opportunistic-infections-in-a-woman-with-gata2-mutation
#14
Andrea Vila, Juan I Dapás, Cynthia V Rivero, Florencia Bocanegra, Roberto F Furnari, Amy P Hsu, Steven M Holland
GATA2 deficiency is a genetic disorder caused by inherited or sporadic haploinsufficient mutations in the GATA2 gene. Patients have abnormalities in hematopoiesis, lymphangiogenesis and immunity; encompassing a broad range of clinical syndromes, mainly characterized by monocytopenia, B and NK cell cytopenia, severe or recurrent infections, and a high risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).We report a case of an Argentinean woman, who presented with multiple opportunistic infections as her first manifestation of GATA2 deficiency...
November 25, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27893351/management-of-iron-overload-in-myelodysplastic-syndromes-combined-deferasirox-and-deferoxamine-in-a-patient-with-liver-disease
#15
Claudio Cerchione, Giuseppe Cerciello, Simona Avilia, Roberta Della Pepa, Novella Pugliese, Marco Picardi, Lucio Catalano, Fabrizio Pane
No abstract text is available yet for this article.
October 24, 2016: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/27892952/dynamic-prognostic-value-of-the-revised-international-prognostic-scoring-system-following-pretransplant-hypomethylating-treatment-in-myelodysplastic-syndrome
#16
S-A Yahng, Y-W Jeon, J-H Yoon, S-H Shin, S-E Lee, Y-S Choi, D-Y Kim, J-H Lee, B-S Cho, K-S Eom, S Lee, C-K Min, H-J Kim, J-W Lee, K-H Lee, W-S Min, J-H Lee, Y-J Kim
This study aimed to analyze the use of the revised International Prognostic Scoring System (IPSS-R) assessed after hypomethylating treatment (HMT) for patients with myelodysplastic syndrome (MDS) undergoing an allogeneic stem cell transplantation (SCT). Among 115 patients who received pre-SCT HMT, comparison analysis of the prognostic values between the IPSS-R at the time of HMT (IPSS-R@HMT) and at the time of SCT after HMT (IPSS-R@SCT) showed a significantly higher predictive power for overall survival (OS) of the latter...
November 28, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27891827/gpx3-methylation-in-bone-marrow-predicts-adverse-prognosis-and-leukemia-transformation-in-myelodysplastic-syndrome
#17
Jing-Dong Zhou, Jiang Lin, Ting-Juan Zhang, Ji-Chun Ma, Lei Yang, Xiang-Mei Wen, Hong Guo, Jing Yang, Zhao-Qun Deng, Jun Qian
Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27890995/endotracheobronchial-lymphoma-two-unusual-case-reports-and-review-of-article
#18
Trilok Chand, Avdhesh Bansal, Harsh Dua, Kapil Sharma
The tracheobronchial origin of non-Hodgkin's lymphoma (NHL) is a very rare presentation, and there are only a few case reports of primary tracheal or endobronchial NHL. We have two cases of primary tracheobronchial NHL; one case was incidentally diagnosed as anaplastic large cell lymphoma of endobronchial origin when a comprehensive workup and surgery were carried out for an endobronchial aspergilloma which was actually sitting on top of lymphoma. The second patient was a case of myelodysplastic syndrome who presented with acute respiratory distress; on thorough workup, he was found to have endotracheal B-cell lymphoma...
November 2016: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/27890256/why-the-stagnation-in-effective-therapy-for-mds
#19
REVIEW
William Blum
The question posed above assumes that we are going nowhere in therapies for myelodysplastic syndromes (MDS) and asks, why? Yet, in recent years novel and effective therapies for MDS indeed have begun to emerge, particularly in patients with lower-risk disease. Beyond this, however, most of the progress has been limited to advances in allogeneic transplantation for higher-risk patients. This discussion will focus first on areas where we have moved beyond "stagnation," including these advances in supportive care for lower-risk patients and in emerging transplant gains...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27888540/higher-dose-of-cd34-peripheral-blood-stem-cells-is-associated-with-better-survival-after-haploidentical-stem-cell-transplantation-in-pediatric-patients
#20
Yao Chen, Lan-Ping Xu, Kai-Yan Liu, Huan Chen, Yu-Hong Chen, Xiao-Hui Zhang, Yu Wang, Feng-Rong Wang, Wei Han, Jing-Zhi Wang, Chen-Hua Yan, Xiao-Jun Huang
Haploidentical stem cell transplantation (SCT) is increasingly used to treat pediatric patients with malignant or non-malignant hematological disorders. The CD34+ dose of bone marrow or peripheral blood stem cells (PBSCs) has been shown to be an important determinant of the transplant outcome in adults under various preparative regimens. However, knowledge of the effect of the CD34+ dose in pediatric haploidentical SCT is limited. We analyzed the data of 348 pediatric patients (aged 2-18 years) with acute or chronic leukemia, myelodysplastic syndrome (MDS), and other hematological disorders that received a transplant between 2002 and 2012...
November 26, 2016: Clinical Transplantation
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