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https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#1
Jason Gotlib
DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29031704/evaluation-of-cooperative-anti-leukemic-effects-of-nilotinib-and-vildagliptin-in-ph-chronic-myeloid-leukemia
#2
Michael Willmann, Irina Sadovnik, Gregor Eisenwort, Martin Entner, Tina Bernthaler, Gabriele Stefanzl, Emir Hadzijusufovic, Daniela Berger, Harald Herrmann, Gregor Hoermann, Peter Valent, Thomas Rülicke
Chronic myeloid leukemia (CML) is a stem cell neoplasm characterized by the BCR/ABL1 oncogene. Although the disease can be kept under control using BCR/ABL1 tyrosine kinase inhibitors (TKI) in most cases, some patients relapse or have resistant disease which points to the need to identify new therapeutic targets in this malignancy. Recent data suggest that leukemic stem cell (LSC) in CML display the SC-mobilizing cell surface enzyme dipeptidyl-peptidase IV (DPPIV=CD26) in an aberrant manner. In the present study, we analyzed the effects of the DPPIV blocker vildagliptin as single agent or in combination with the BCR/ABL1 TKI imatinib or nilotinib on growth and survival of CML LSC in vitro and on LSC engraftment in an in vivo xenotransplantation NSG mouse model...
October 12, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29030335/single-cell-rna-seq-reveals-a-distinct-transcriptome-signature-of-aneuploid-hematopoietic-cells
#3
Xin Zhao, Shouguo Gao, Zhijie Wu, Sachiko Kajigaya, Xingmin Feng, Qingguo Liu, Danielle M Townsley, James Cooper, Jinguo Chen, Keyvan Keyvanfar, Maria Del Pilar Fernandez Ibanez, Xujing Wang, Neal S Young
Cancer cells frequently exhibit chromosomal abnormalities. Specific cytogenetic aberrations often are predictors of outcome, especially in hematologic neoplasms, as for example monosomy 7 in myeloid malignancies. The functional consequences of aneuploidy at the cellular level are difficult to assess, due to lack of convenient markers to distinguish abnormal from diploid cells. We performed single-cell RNA sequencing (scRNA-seq) to study hematopoietic stem and progenitor cells (HSPCs) from the bone marrow of four healthy donors and of five patients with bone marrow failure and chromosome gain or loss...
October 13, 2017: Blood
https://www.readbyqxmd.com/read/29025689/soho-state-of-the-art-update-and-next-questions-biology-and-treatment-of-myelodysplastic-syndromes
#4
REVIEW
David A Sallman, Tiffany N Tanaka, Alan List, Rafael Bejar
Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by clonal hematopoiesis leading to bone marrow dysplasia and cytopenias. Recently, significant advancements have been made in understanding the pathogenic mechanisms of this disease. In particular, how a wide array of somatic mutations can induce a common clinical phenotype has been investigated. Specifically, activation of innate immune signaling (i.e. myeloid derived suppressor cells) and the NLRP3 inflammasome in hematopoietic stem/progenitor cells play a central role in the biology of MDS, leading to pyroptotic cell death and clonal expansion...
October 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29025601/a-neoplasm-with-fip1l1-pdgfra-fusion-presenting-as-pediatric-t-cell-lymphoblastic-leukemia-lymphoma-without-eosinophilia
#5
Matthew J Oberley, Christopher Denton, Jianling Ji, Matthew Hiemenz, Deepa Bhojwani, Dejerianne Ostrow, Samuel Wu, Paul Gaynon, Gordana Raca
The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025591/identification-of-a-novel-csf3r-sptan1-fusion-gene-in-an-atypical-chronic-myeloid-leukemia-patient-with-t-1-9-p34-q34-by-rna-seq
#6
Guangying Sheng, Jian Zhang, Zhao Zeng, Jinlan Pan, Qinrong Wang, Lijun Wen, Yang Xu, Depei Wu, Suning Chen
Membrane-proximal and truncated mutations of colony-stimulating factor 3 receptor (CSF3R) are frequently found in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). However, rearrangement involving CSF3R in hematological neoplasms has not been reported. Here, we report a case of a 21-year-old female diagnosed as aCML with t(1;9)(p34;q34) who presented a CSF3R rearrangement. First, RNA sequencing identified a novel fusion transcript involving exon 17 of CSF3R and exon 50 of non-erythrocytic-1-spectrin-alpha (SPTAN1)...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025582/a-novel-trip11-flt3-fusion-in-a-patient-with-a-myeloid-lymphoid-neoplasm-with-eosinophilia
#7
Alfred Chung, Yanli Hou, Robert S Ohgami, Ann Von Gehr, Dianna G Fisk, Krishna M Roskin, Xu Li, Linda Gojenola, Charles D Bangs, Daniel A Arber, Andrew Z Fire, Athena M Cherry, James L Zehnder, Jason Gotlib, Jason D Merker
FLT3 fusions are associated with myeloid and lymphoid neoplasms with eosinophilia. We describe a patient presenting with clinicopathologic features of both chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) and systemic mastocytosis (SM). The bone marrow demonstrated a myeloproliferative neoplasm with eosinophilia and aggregates of atypical mast cells. Cytogenetic analysis revealed a t(13;14)(q12;q32), which was subsequently molecularly characterized as a novel TRIP11-FLT3 rearrangement. A KIT D816V mutation was also identified...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29023992/therapy-related-chronic-myelomonocytic-leukemia-cmml-molecular-cytogenetic-and-clinical-distinctions-from-de-novo-cmml
#8
Mrinal M Patnaik, Rangit Vallapureddy, Fevzi F Yalniz, Curtis A Hanson, Rhett P Ketterling, Terra L Lasho, Christy Finke, Aref Al-Kali, Naseema Gangat, Ayalew Tefferi
Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n=497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy...
October 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28983777/therapy-for-chronic-myelomonocytic-leukemia-in-a-new-era
#9
REVIEW
Tamara K Moyo, Michael R Savona
Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined...
October 6, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28982745/nccn-guidelines-insights-myeloproliferative-neoplasms-version-2-2018
#10
Ruben A Mesa, Catriona Jamieson, Ravi Bhatia, Michael W Deininger, Christopher D Fletcher, Aaron T Gerds, Ivana Gojo, Jason Gotlib, Krishna Gundabolu, Gabriela Hobbs, Brandon McMahon, Sanjay R Mohan, Stephen Oh, Eric Padron, Nikolaos Papadantonakis, Philip Pancari, Nikolai Podoltsev, Raajit Rampal, Erik Ranheim, Vishnu Reddy, Lindsay A M Rein, Bart Scott, David S Snyder, Brady L Stein, Moshe Talpaz, Srdan Verstovsek, Martha Wadleigh, Eunice S Wang, Mary Anne Bergman, Kristina M Gregory, Hema Sundar
Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28978863/myeloid-neoplasms-in-the-world-health-organization-2016-classification
#11
Norio Asou
In the 2016 revision of the World Health Organization (WHO) classification, the categories of myeloid neoplasms have not been revised significantly from the 2008 fourth edition. However, recent discovery of molecular abnormalities provides a new perspective regarding the diagnostic and prognostic markers. In myeloproliferative neoplasms, the identification of CALR gene mutation, in addition to the JAK2 and MPL mutations, has impacted the diagnostic criteria. In myelodysplastic syndromes and acute myeloid leukemia, in addition to alterations in the transcription factors and signal transduction pathways, discovery of gene mutations in the epigenetic regulators that are involved in DNA methylation, histone modification, cohesin complex, and RNA splicing, by comprehensive genetic analyses, has improved our understanding of the pathobiology of these diseases...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978828/familial-hematological-malignancies
#12
Shinsuke Hirabayashi, Atsushi Manabe
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. The study of cancer genomes has identified inherited genetic drivers that predispose cancer cells to clonal evolution. The revisions in the categories of myeloid neoplasms and acute leukemia were published as a monograph in 2016. We described familial hematological malignancies using the 2016 edition of the WHO classification.
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28975067/diagnostic-and-therapeutic-implications-of-genetic-heterogeneity-in-myeloid-neoplasms-uncovered-by-comprehensive-mutational-analysis
#13
Sarah M Choi, Ben Goldenson, Lo Ann Peterson, Shira Dinner, Brady L Stein, Amir Behdad
While growing use of comprehensive mutational analysis has led to the discovery of innumerable genetic alterations associated with various myeloid neoplasms, the under-recognized phenomenon of genetic heterogeneity within such neoplasms creates a potential for diagnostic confusion. Here, we describe two cases where expanded mutational testing led to amendment of an initial diagnosis of chronic myelogenous leukemia with subsequent altered treatment of each patient. We demonstrate the power of comprehensive testing in ensuring appropriate classification of genetically heterogeneous neoplasms, and emphasize thoughtful analysis of molecular and genetic data as an essential component of diagnosis and management...
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28973700/hematologic-malignancies-discovered-on-investigation-of-breast-abnormalities
#14
Alaa Alsadi, Dianna Lin, Hussein Alnajar, Arlen Brickman, Colin Martyn, Paolo Gattuso
OBJECTIVES: Hematological malignancies of the breast share a presentation similar to primary breast carcinomas but differ substantially in therapeutic approach and clinical outcomes. In this study, we investigate the frequency of hematological malignancies, their relative primary and secondary occurrences, and further characterize the distinct histopathologies of these malignancies with a special focus on lymphomas. To our knowledge this is one of the largest and most comprehensive studies of breast hematologic malignancies...
October 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28970467/systemic-mastocytosis-in-association-with-small-lymphocytic-lymphoma
#15
Muhammad F Iqbal, Paolo Marco K Soriano, Sanjai Nagendra, Sherjeel Sana
BACKGROUND Systemic mastocytosis with an associated hematologic non-mast cell lineage disease is a rare entity, and the majority of systemic mastocytosis cases are associated with myeloid neoplasm. Lymphoproliferative disorders are less commonly associated with systemic mastocytosis and a few cases of systemic mastocytosis associated with chronic lymphocytic leukemia have been described in the literature. CASE REPORT We present a case of indolent systemic mastocytosis associated with small lymphocytic lymphoma...
October 3, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28964959/genetic-variations-of-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-leukemia-and-myelodysplastic-syndrome-by-targeted-deep-sequencing
#16
Kenko Azuma, Tomohiro Umezu, Satoshi Imanishi, Michiyo Asano, Seiichiro Yoshizawa, Seiichiro Katagiri, Kazuma Ohyashiki, Junko H Ohyashiki
Bone marrow mesenchymal stromal cells (MSCs), which support proliferation and differentiation of hematopoietic stem cells, may play a crucial role in the pathogenesis of myeloid neoplasms. To determine whether MSCs in myeloid neoplasms harbor distinct somatic mutations that may affect their function, we used a targeted gene sequencing panel containing 50 myeloid neoplasm-associated genes with coverage of ≥500. We compared the genetic alterations between MSCs and bone marrow hematopoietic (BM) cells from patients with acute leukemia (n=5) or myelodysplastic syndrome (MDS, n=5)...
September 21, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28960095/midostaurin-treatment-in-flt3-mutated-acute-myeloid-leukemia-and-systemic-mastocytosis
#17
Sabine Kayser, Mark J Levis, Richard F Schlenk
A number of tyrosine kinase inhibitors (TKIs) have been developed that inhibit the constitutively activated kinase activity caused by activating tyrosine kinase mutations, such as FLT3 or KIT, thus interrupting signaling pathways. Currently, midostaurin is the only approved TKI as monotherapy for aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia displaying a KIT mutation as well as in combination with standard intensive chemotherapy for adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML)...
September 29, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28955657/familial-myelodysplastic-acute-leukemia-syndromes-myeloid-neoplasms-with-germline-predisposition
#18
REVIEW
Renata Lyrio Rafael Baptista, Anna Cláudia Evangelista Dos Santos, Luciana Mayumi Gutiyama, Cristiana Solza, Ilana Renault Zalcberg
Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28954105/episodic-angioedema-associated-with-eosinophilia
#19
Fang Liu, Wenxing Hu, Haibo Liu, Min Zhang, Hong Sang
We report a 12-year-old girl who presented with recurrent angioedema on the face, trunk, and extremities, and concomitant marked weight gain for 5 years. During the episode, her white blood cell count increased to 47.7×109/L with 89.9% eosinophils, followed by elevated serum level of IL-5, IgE, IgM, and LDH. Histopathology showed perivascular eosinophilic infiltration and diffuse eosinophilic infiltration throughout the dermis. Possible causes of hypereosinophilia and eosinophilic infiltration of vital organs were ruled out...
July 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28937778/-changes-of-the-who-classification-of-myeloid-neoplasms-in-the-context-of-the-2016-revision
#20
Juraj Marcinek, Tomáš Balhárek, Lukáš Plank
Continual progress of knowleges in hematopathology and genetics of hematologic tumors requires actualisation of widely accepted and presently used WHO classification of myeloid neoplasms published 8 years ago. However, the basic principles of this classification remain unchanged, therefore the authors of new WHO classification mention the "revision" of previous and not the introduction o new classification. The aim of this paper is to outline the most important changes of myeloid neoplasm diagnostics to pathologists, hematologists and other clinicians in Czech Republic and Slovakia...
2017: Ceskoslovenská Patologie
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