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Myeloid neoplasm

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https://www.readbyqxmd.com/read/29455651/targeting-few-to-help-hundreds-jak-mapk-and-rock-pathways-as-druggable-targets-in-atypical-chronic-myeloid-leukemia
#1
REVIEW
Stefania Rocca, Giovanna Carrà, Pietro Poggio, Alessandro Morotti, Mara Brancaccio
Atypical Chronic Myeloid Leukemia (aCML) is a myeloproliferative neoplasm characterized by neutrophilic leukocytosis and dysgranulopoiesis. From a genetic point of view, aCML shows a heterogeneous mutational landscape with mutations affecting signal transduction proteins but also broad genetic modifiers and chromatin remodelers, making difficult to understand the molecular mechanisms causing the onset of the disease. The JAK-STAT, MAPK and ROCK pathways are known to be responsible for myeloproliferation in physiological conditions and to be aberrantly activated in myeloproliferative diseases...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455318/expression-of-terminal-deoxynucleotidyl-transferase-tdt-in-classical-seminoma-a-potential-diagnostic-pitfall
#2
Alexander Brobeil, Florian Wagenlehner, Stefan Gattenlöhner
Seminomas are the most frequent testicular tumors and in spite of specific markers some histological subtypes can be diagnostically challenging due to the potential overlap of morphologic features and a variant antigen expression. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in hematogones, thymic T cells, lymphoblastic lymphoma/leukemia (LBL), and in some cases of acute myeloid leukemia but so far has not been described to be expressed in seminomas. After observing a reactivity of TdT in one case of seminoma, we analyzed ten additional tumors by immunohistochemistry to determine their spectrum of reactivity for TdT...
February 18, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29455234/blastic-plasmacytoid-dendritic-cell-neoplasm-update-on-therapy-especially-novel-agents
#3
REVIEW
Shunan Wang, Xingtong Wang, Mingsuo Liu, Ou Bai
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. Most patients present with asymptomatic skin lesions as the first symptom and has a high frequency of bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co-expression without common lymphoid or myeloid lineage markers. There is no consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive to chemotherapy but the median event-free survival is very short...
February 17, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29454474/cardiovascular-pulmonary-and-metabolic-toxicities-complicating-tyrosine-kinase-inhibitor-therapy-in-chronic-myeloid-leukemia-strategies-for-monitoring-detecting-and-managing
#4
REVIEW
Bruno C Medeiros, Jennifer Possick, Michael Fradley
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. Beyond matching patient disease profiles with TKI specificity, differences in the efficacy and toxicity profiles and a patient's comorbid risk factors should be considered when selecting the most appropriate agent. Our objectives are to review the incidence and severity of cardiovascular, metabolic, and pulmonary disorders associated with these TKIs, highlighting differences in adverse event profiles, suggested risk-mitigation strategies, and guidance for TKI selection in different settings...
February 3, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29428448/pulmonary-langerhans-cell-histiocytosis-acute-myeloid-leukemia-and-myelofibrosis-in-a-large-family-and-review-of-the-literature
#5
Matthew P Blakley, Janice P Dutcher, Peter H Wiernik
BACKGROUND: There is mounting evidence that Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are hematopoietic neoplasms that arise from the same myeloid precursor cell. In addition, studies suggest a relationship between LCH and primary idiopathic myelofibrosis (MF). Furthermore familial LCH, AML, and MF have each been reported. METHODS: We examined more than 750 pedigrees of familial hematologic malignancies for evidence of familial LCH, AML, and/or MF and identified one family with all three neoplasms, which is presented here...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29427319/distinguishing-myelofibrosis-from-polycythemia-vera-and-essential-thrombocythemia-the-utility-of-enumerating-circulating-stem-cells-with-aberrant-hmicl-expression-by-flow-cytometry
#6
L L Herborg, L Nederby, H C Hasselbalch, A Aggerholm, A S Roug
INTRODUCTION: Diagnosing BCR-ABL negative myeloproliferative neoplasms (MPN) may be challenging due to overlapping features and lack of robust discriminatory parameters, especially between essential thrombocythemia (ET) and prefibrotic myelofibrosis (MF). Circulating immature hematopoietic cells are variably present in polycythemia vera (PV), ET, and MF. The C-type lectin hMICL is aberrantly expressed on hematopoietic stem cells in the majority of acute myeloid leukemia patients. However, the hMICL expression in MPN, having varying propensity of leukemic transformation, is unsettled...
February 10, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29426921/the-2016-who-classification-and-diagnostic-criteria-for-myeloproliferative-neoplasms-document-summary-and-in-depth-discussion
#7
REVIEW
Tiziano Barbui, Jürgen Thiele, Heinz Gisslinger, Hans Michael Kvasnicka, Alessandro M Vannucchi, Paola Guglielmelli, Attilio Orazi, Ayalew Tefferi
The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category...
February 9, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29424411/-blastic-plasmacytoid-dendritic-cell-neoplasm-report-of-three-cases
#8
Alejandro Avilés-Salas, Myrna Candelaria, Mayra Ponce, Abraham Cañavera-Constantino, Sebastián Burgos
Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination...
September 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/29423555/second-malignancies-after-hematopoietic-stem-cell-transplantation
#9
REVIEW
Ivetta Danylesko, Avichai Shimoni
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5-10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers...
February 8, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29417354/clonal-dynamics-in-a-case-of-acute-monoblastic-leukemia-that-later-developed-myeloproliferative-neoplasm
#10
Shinya Sato, Hidehiro Itonaga, Masataka Taguchi, Yasushi Sawayama, Daisuke Imanishi, Hideki Tsushima, Tomoko Hata, Yukiyoshi Moriuchi, Hiroyuki Mishima, Akira Kinoshita, Koh-Ichiro Yoshiura, Yasushi Miyazaki
In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations...
February 7, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29411417/chronic-myeloid-leukemia-2018-update-on-diagnosis-therapy-and-monitoring
#11
Elias Jabbour, Hagop Kantarjian
DISEASE OVERVIEW: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. DIAGNOSIS: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome...
March 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29411299/a-rare-calr-variant-mutation-and-a-review-of-calr-in-essential-thrombocythemia
#12
Robert Diep, Ara Metjian
Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm characterized by megakaryocyte hyperplasia, thrombocytosis, thrombotic and hemorrhagic complications, and potential transformation into myelofibrosis and acute myeloid leukemia. The vast majority of cases are driven by a somatic mutation in JAK2, CALR, or MPL. CALR, a gene that codes for the calcium-binding chaperone calreticulin, is the predominant mutation in patients with non-mutated JAK2 essential thrombocythemia, accounting for 20-25% of the overall somatic mutation frequency in ET...
February 6, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29407586/8q24-myc-rearrangement-is-a-recurrent-cytogenetic-abnormality-in-blastic-plasmacytoid-dendritic-cell-neoplasms
#13
Prajwal C Boddu, Sa A Wang, Naveen Pemmaraju, Zhenya Tang, Shimin Hu, Shaoying Li, Jie Xu, L Jeffrey Medeiros, Guilin Tang
8q24/MYC rearrangements resulting in MYC overexpression occur most frequently in lymphoid neoplasms. MYC rearrangements rarely have been described in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Over an 8-year period in our hospital, 5 of 41 (12%) patients with BPDCN were shown 8q24/MYC rearrangements, including 2 with t(6;8)(p21;q24), 1 with t(8;14)(q24;q32), 1 with t(X;8)(q24;q24), and 1 with t(3;8)(p25;q24). 8q24/MYC rearrangement was present in the stemline in 4 patients and in the sideline in one; the latter was a patient with primary myelofibrosis who then developed BPDCN...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29405993/molecular-approaches-identify-a-cryptic-mecom-rearrangement-in-a-child-with-a-rapidly-progressive-myeloid-neoplasm
#14
Roberto R Capela de Matos, Moneeb A K Othman, Gerson M Ferreira, Elaine S Costa, Joana B Melo, Isabel M Carreira, Mariana T de Souza, Bruno A Lopes, Mariana Emerenciano, Marcelo G P Land, Thomas Liehr, Raul C Ribeiro, Maria Luiza M Silva
Myeloid neoplasms are a heterogeneous group of hematologic disorders with divergent patterns of cell differentiation and proliferation, as well as divergent clinical courses. Rare recurrent genetic abnormalities related to this group of cancers are associated with poor outcomes. One such abnormality is the MECOM gene rearrangement that typically occurs in cases with chromosome 7 abnormalities. MECOM encodes a transcription factor that plays an essential role in cell proliferation and maintenance and also in epigenetic regulation...
February 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29403218/fine-needle-aspiration-cytology-of-granulocytic-sarcoma-presenting-as-a-breast-lump-report-of-a-rare-case-with-a-comprehensive-literature-search
#15
Abhishek Sharma, Anjan Kr Das, Subrata Pal, Subodh Bhattacharyya
Myeloid sarcoma is a neoplasm of myeloid cells that can arise before or concurrent with or may follow acute myeloid leukemia. Very rarely, it can present as an isolated breast lump. We have diagnosed a case of myeloid sarcoma by fine-needle aspiration cytology (FNAC), in a 52-year-old woman who presented with the right-sided breast lump. FNAC showed hypercellular smears with immature myeloid cells few neutrophils and many large round cells with high nuclear-cytoplasmic ratio, prominent nucleoli and a moderate amount of granular cytoplasm...
January 2018: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/29403082/a-reevaluation-of-erythroid-predominance-in-acute-myeloid-leukemia-using-the-updated-who-2016-criteria
#16
Elizabeth Margolskee, Geoff Mikita, Bryan Rea, Adam Bagg, Zhuang Zuo, Yi Sun, Maitrayee Goswami, Sa A Wang, Jean Oak, Daniel A Arber, M Brandon Allen, Tracy I George, Heesun J Rogers, Eric Hsi, Robert P Hasserjian, Attilio Orazi
The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO...
February 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29387948/expression-of-hippo-signaling-pathway-and-aurora-kinase-genes-in-chronic-myeloid-leukemia
#17
Ana Paula Zambuzi Cardoso Marsola, Belinda Pinto Simões, Leonardo Carvalho Palma, Maria Gabriela Berzoti-Coelho, Sandra Mara Burin, Fabíola Attié de Castro
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from clonal expansion of hematopoietic stem cells positive for the Philadelphia chromosome. The CML pathogenesis is associated with expression of the BCR-ABL1 oncogene, which encodes the Bcr-Abl protein with tyrosine kinase activity, promoting the leukemic cell exacerbated myeloproliferation and resistance to apoptosis. CML patients are usually treated with tyrosine kinase inhibitors (TKI), but some of them acquire resistance or are refractory to TKI...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29378171/discriminating-myelodysplastic-syndrome-and-other-myeloid-malignancies-from-non-clonal-disorders-by-multiparametric-analysis-of-automated-cell-data
#18
Seon Young Kim, Yumi Park, Hyunjin Kim, Jimyung Kim, Gye Cheol Kwon, Sun Hoe Koo
BACKGROUND: We investigated the usefulness of novel complete blood count (CBC) data for discriminating myeloid malignancies from non-clonal CBC abnormalities. METHODS: Data were obtained during routine CBC tests of 119 samples from 37 myelodysplastic syndrome (MDS) patients, 92 samples from 45 myeloproliferative neoplasm (MPN) patients, and 15 samples from 11 chronic myelogenous leukemia (CML) patients using a DxH800 (Beckman Coulter). Data obtained from patients with hypocellular bone marrow and from those with other non-clonal diseases with CBC abnormalities were included in the comparisons...
January 26, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29372845/myeloid-neoplasm-with-germline-predisposition-a-2016-update-for-pathologists
#19
Juehua Gao, Shunyou Gong, Yi-Hua Chen
CONTEXT: - Myeloid neoplasms with familial occurrence have been rarely reported in the past. With the advance of molecular technology and better understanding of the molecular pathogenesis of myeloid neoplasms, investigating the genetic causes of familial acute myeloid leukemia or myelodysplastic syndrome has become feasible in the clinical setting. Recent studies have identified a rapidly expanding list of germline mutations associated with increased risks of developing myeloid neoplasm in the affected families...
January 26, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29355841/jak2-idh-mutant-driven-myeloproliferative-neoplasm-is-sensitive-to-combined-targeted-inhibition
#20
Anna Sophia McKenney, Allison N Lau, Amritha Varshini Hanasoge Somasundara, Barbara Spitzer, Andrew M Intlekofer, Jihae Ahn, Kaitlyn Shank, Franck T Rapaport, Minal A Patel, Efthymia Papalexi, Alan H Shih, April Chiu, Elizaveta Freinkman, Esra A Akbay, Mya Steadman, Raj Nagaraja, Katharine Yen, Julie Teruya-Feldstein, Kwok-Kin Wong, Raajit Rampal, Matthew G Vander Heiden, Craig B Thompson, Ross L Levine
Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617F and mutant IDH1R132H or Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617F Idh2R140Q-mutant MPNs were sensitive to small-molecule inhibition of IDH...
February 1, 2018: Journal of Clinical Investigation
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