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Myelodysplastic syndrom

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https://www.readbyqxmd.com/read/28648154/-the-cause-of-cytopenia-of-undetermined-significance-can-often-be-found-by-using-next-generation-sequencing
#1
Jakob Werner Hansen, Simon Husby, Kirsten Grønbæk
Patients with persistent cytopenia are frequently referred to the haematological departments , and a diagnosis of myelodysplastic syndrome is often suspected. After routine assessment including a broad range of blood tests, bone marrow biopsy, and cytogenetics, a definite diagnosis can still not be found for some patients, although they have symptomatic cytopenia. In these cases, next generation sequencing is a valuable supplement in identifying patients with early stages of myeloid cancer.
June 19, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28645270/qualitative-modification-and-development-of-patient-and-caregiver-reported-outcome-measures-for-iron-chelation-therapy
#2
Erica G Horodniceanu, Vasudha Bal, Harman Dhatt, John A Carter, Vicky Huang, Kathryn Lasch
BACKGROUND: Compliance, palatability, gastrointestinal (GI) symptom, and treatment satisfaction patient- and observer-reported outcome (PRO, ObsRO) measures were developed/modified for patients with transfusion-dependent anemias or myelodysplastic syndrome (MDS) requiring iron chelation therapy (ICT). METHODS: This qualitative cross-sectional observational study used grounded theory data collection and analysis methods and followed PRO/ObsRO development industry guidance...
June 23, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28645262/acute-myeloid-leukemia-and-pregnancy-clinical-experience-from-a-single-center-and-a-review-of-the-literature
#3
Nicola Stefano Fracchiolla, Mariarita Sciumè, Francesco Dambrosi, Francesca Guidotti, Manuela Wally Ossola, Giovanna Chidini, Umberto Gianelli, Daniela Merlo, Agostino Cortelezzi
BACKGROUND: Acute myeloid leukemia (AML) accounts for more than two thirds of leukemia during pregnancy and has an incidence of 1 in 75,000 to 100,000. Its clinical management remains a challenging therapeutic task both for patient and medical team, given to the therapy-attributable risks for mother and fetus and the connected counseling regarding pregnancy continuation. METHODS: We provided a review of updated literature and a comprehensive description of five maternal/fetal outcomes of AML cases diagnosed concomitantly to pregnancy and treated at our Institution from 2006 to 2012...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28645118/outcome-of-patients-treated-for-myelodysplastic-syndromes-with-5q-deletion-after-failure-of-lenalidomide-therapy
#4
Thomas Prebet, Thomas Cluzeau, Sophie Park, Mikkael A Sekeres, Ulrich Germing, Lionel Ades, Uwe Platzbecker, Katharina Gotze, Norbert Vey, Esther Oliva, Mary M Sugrue, Cecile Bally, Charikleia Kelaidi, Najla Al Ali, Pierre Fenaux, Steven D Gore, Rami Komrokji
While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 patient cases of lower-risk MDS patients with 5q deletion and to analyze their outcome after failure of lenalidomide...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#5
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#6
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28643018/heterogeneity-of-gata2-related-myeloid-neoplasms
#7
REVIEW
Shinsuke Hirabayashi, Marcin W Wlodarski, Emilia Kozyra, Charlotte M Niemeyer
The GATA2 gene codes for a master hematopoietic transcription factor that is essential for the proliferation and maintenance of hematopoietic stem and progenitor cells. Heterozygous germline mutations in GATA2 have been initially associated with several clinical entities that are now collectively defined as GATA2 deficiency. Despite pleiotropic clinical manifestations, the high propensity for the development of myelodysplastic syndromes (MDS) constitutes the most common clinical denominator of this major MDS predisposition syndrome...
June 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28642604/turning-the-tide-in-myelodysplastic-myeloproliferative-neoplasms
#8
REVIEW
Michael W N Deininger, Jeffrey W Tyner, Eric Solary
Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) are aggressive myeloid malignancies recognized as a distinct category owing to their unique combination of dysplastic and proliferative features. Although current classification schemes still emphasize morphology and exclusionary criteria, disease-defining somatic mutations and/or germline predisposition alleles are increasingly incorporated into diagnostic algorithms. The developing picture suggests that phenotypes are driven mostly by epigenetic mechanisms that reflect a complex interplay between genotype, physiological processes such as ageing and interactions between malignant haematopoietic cells and the stromal microenvironment of the bone marrow...
June 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28642303/molecular-analysis-of-myelodysplastic-syndrome-with-isolated-del-5q-reveals-a-specific-spectrum-of-molecular-mutations-with-prognostic-impact-a-study-on-123-patients-and-27-genes
#9
Manja Meggendorfer, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, giving with morphological features the diagnosis of myelodysplastic syndrome with isolated del(5q). These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia. However, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated del(5q) diagnosed following the World Health Organization classifications 2008 and 2016 by sequencing 27 genes...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28642072/recombinant-human-thrombopoietin-promotes-platelet-engraftment-and-improves-prognosis-of-patients-with-myelodysplastic-syndromes-and-aplastic-anemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#10
Hong Wang, Man Huang, Ying Zhao, Jia-Qian Qi, Chun Chen, Ya-Qiong Tang, Hui-Ying Qiu, Cheng-Cheng Fu, Xiao-Wen Tang, De-Pei Wu, Chang-Geng Ruan, Yue Han
Poor platelet graft function (PPGF) is a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no optimal treatment has been recommended. This study investigated aspects of platelet recovery after allo-HSCT, including prognostic value and the effect of recombinant human thrombopoietin (rhTPO). We retrospectively analyzed 275 patients who received allo-HSCT in our center. Of them, 135 (49.1%) patients had good platelet graft function (GPGF) and 140 (50.9%) had PPGF...
June 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28641645/-subtype-and-functional-biomarker-changes-of-nk-cells-in-peripheral-blood-of-patients-with-myelodysplastic-syndrome
#11
Shu-Juan Xu, Zong-Hong Shao, Rong Fu, Hua-Quan Wang, Hui Liu, Chun-Yan Liu, Wei Zhang
OBJECTIVE: To analyze the subtype and functional biomarker expression changes of natural kill cells(NK) in peripheral blood of patients with myelodysplastic syndrome(MDS) and normal people, so as to evaluate the relationships between these changes and hematopoietic functions and to explore the role of NK cells in the pathogenesis of MDS. METHODS: The quantity of NK cells and the expression of biomarkers(NKp30,NKp46,NKG2A) on NK cells were detected by flow cytometry in 35 MDS patients from 2015 to 2016 in our hospital and 34 normal controls...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28639327/acute-leukemic-transformation-of-myelodysplastic-syndrome-is-cytochemistry-still-relevant
#12
Imogen Caldwell, Anna Ruskova, Nicola Eaddy, Barbara J Bain
No abstract text is available yet for this article.
June 22, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#13
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#14
Marcin W Wlodarski, Matthew Collin, Marshall S Horwitz
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637620/runx1-deficiency-familial-platelet-disorder-with-predisposition-to-myeloid-leukemia-fpdmm
#15
REVIEW
Brigitte Schlegelberger, Paula G Heller
In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelets; (2) functional platelets defects leading to prolonged bleeding; and (3) an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL)...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637619/practical-considerations-for-diagnosis-and-management-of-patients-and-carriers
#16
REVIEW
Charlotte M Niemeyer, Cristina Mecucci
Newly diagnosed children and adults with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) need to be screened for presence of a genetic predisposition syndrome because the information on the genetic status is likely to influence clinical care and management of the patient and the family. Scenarios in which genetic counseling is advised include presence of a mutation on somatic screen that can be associated with a germline predisposition, hematologic or cytogenetic characteristics suggestive of an underlying susceptibility syndrome, non-hematological phenotype suspicious for a familial condition, history of previous malignancy, or a family history of cancer, cytopenia, autoimmunity, or organ-system manifestation fitting a predisposition syndrome...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637614/classical-inherited-bone-marrow-failure-syndromes-with-high-risk-for-myelodysplastic-syndrome-and-acute-myelogenous-leukemia
#17
REVIEW
Sharon A Savage, Carlo Dufour
The inherited marrow failure syndromes (IBMFS) are a heterogeneous group of diseases characterized by failure in the production of one or more blood lineage. The clinical manifestations of the IBMFS vary according to the type and number of blood cell lines involved, including different combinations of anemia, leukopenia, and thrombocytopenia. In some IBMFS, systemic non-hematologic manifestations, including congenital malformations, mucocutaneous abnormalities, developmental delay, and other medical complications, may be present...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28636974/sema3a-partially-reverses-vegf-effects-through-binding-to-neuropilin-1
#18
Bruna Palodetto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Flavia Adolfo Corrocher, Fernanda Marconi Roversi, Fernanda Soares Niemann, Karla Priscila Vieira Ferro, Ana Leda Figueiredo Longhini, Paula Melo Campos, Patricia Favaro, Sara Teresinha Olalla Saad
Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34(+) HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls...
June 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28635156/pyoderma-gangrenosum-and-underlying-diseases-in-japanese-patients-a-regional-long-term-study
#19
Sae Inoue, Jun-Ichi Furuta, Yasuhiro Fujisawa, Saori Onizawa, Shusaku Ito, Masayuki Sakiyama, Keiko Kobayashi, Toshiyuki Kanou, Shigeruko Iijima, Tsunao Ohi, Chimaki Okubo, Yoshihiro Moriyama, Naoko Okiyama, Manabu Fujimoto
Pyoderma gangrenosum (PG) is a chronic inflammatory disease of unknown cause that presents as an inflammatory and ulcerative disorder of the skin. PG is often associated with an underlying systemic disease. However, the frequencies of the underlying diseases are unclear in Japanese patients. In this retrospective, observational study, all patients diagnosed with PG who visited dermatology departments of nine regional hospitals in and around Ibaraki Prefecture were collected from 1982 to 2011 or 2014. The diagnoses of PG were based on the characteristic clinical and histological appearances and ruling out of infection...
June 21, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28634182/sf3b1-initiating-mutations-in-mds-with-ring-sideroblasts-target-lymphomyeloid-hematopoietic-stem-cells
#20
Teresa Mortera-Blanco, Marios Dimitriou, Petter S Woll, Mohsen Karimi, Edda Elvarsdottir, Simona Conte, Magnus Tobiasson, Monika Jansson, Iyadh Douagi, Matahi Moarii, Leonie Saft, Elli Papaemmanuil, Sten Eirik W Jacobsen, Eva Hellström-Lindberg
Mutations in the RNA splicing gene SF3B1 are found in more than 80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients, and were also present in downstream myeloid and erythroid progenitor cells...
June 20, 2017: Blood
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