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Myeloid neoplasia

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https://www.readbyqxmd.com/read/29132164/mutational-spectrum-of-fanconi-anemia-associated-myeloid-neoplasms
#1
Mwe Mwe Chao, Kathrin Thomay, Gudrun Goehring, Marcin Wlodarski, Victor Pastor, Brigitte Schlegelberger, Detlev Schindler, Christian Peter Kratz, Charlotte Niemeyer
Individuals with Fanconi anemia (FA) have a high risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), yet the secondary somatic mutations lending to these malignancies remain to be further elucidated. We employed a next-generation sequencing myeloid neoplasia gene panel to determine the mutational spectrum of FA-related MDS/AML. Ten of 16 patients showed missense, nonsense, insertion or duplication mutations in 13 genes. In contrast to findings in MDS in the general population, mutations in genes involved in RNA splicing were rarely affected...
November 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/29123956/mutations-in-jak2-and-calreticulin-genes-are-associated-with-specific-alterations-of-the-immune-system-in-myelofibrosis
#2
Marco Romano, Daria Sollazzo, Sara Trabanelli, Martina Barone, Nicola Polverelli, Margherita Perricone, Dorian Forte, Simona Luatti, Michele Cavo, Nicola Vianelli, Camilla Jandus, Francesca Palandri, Lucia Catani
Myelofibrosis (MF) is a clonal neoplasia associated with chronic inflammation due to aberrant cytokine production. Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway. Since this pathway is essential in shaping the immune response, we investigated the role of circulating immune subsets and cytokines in 38 patients (20 carrying JAK2((V617F)),13 exon-9 CALR mutation and 5 triple negative)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29108292/azacitidine-or-intensive-chemotherapy-for-older-patients-with-secondary-or-therapy-related-acute-myeloid-leukemia
#3
Pierre-Yves Dumas, Sarah Bertoli, Emilie Bérard, Clémence Médiavilla, Edwige Yon, Suzanne Tavitian, Thibaut Leguay, Françoise Huguet, Edouard Forcade, Noël Milpied, Audrey Sarry, Mathieu Sauvezie, Pierre Bories, Arnaud Pigneux, Christian Récher
The treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.5% post-myelodysplastic syndrome, 17.4% post-myeloproliferative neoplasia, and 45.1% therapy-related acute myeloid leukemia. Patients treated by chemotherapy had less adverse cytogenetics, higher white blood-cell counts, and were younger: the latter two being independent factors entered into the multivariate analyses...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107340/langerhans-cell-histiocytosis-a-neoplastic-disorder-driven-by-ras-erk-pathway-mutations
#4
REVIEW
Gary Tran, Thy N Huynh, Amy S Paller
Langerhans cell histiocytosis (LCH) is a disorder of myeloid neoplasia of dendritic cells that affects 1 in 200,000 children <15 years of age and even fewer adults. LCH presents with a spectrum of clinical manifestations. High-risk stratification is reserved for infiltration of blood, spleen, liver, and lungs. After decades of debate on the disease pathogenesis, a neoplastic mechanism is now favored on the basis of LCH cell clonality, rare cases of familial clustering, and recent evidence of mutations involving the Ras/Raf/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway in lesional biopsy specimens...
October 26, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29064023/diagnostic-and-prognostic-utility-of-fluorescence-in-situ-hybridization-fish-analysis-in-acute-myeloid-leukemia
#5
REVIEW
Patrick R Gonzales, Fady M Mikhail
PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a hematologic neoplasia consisting of incompletely differentiated hematopoietic cells of the myeloid lineage that proliferate in the bone marrow, blood, and/or other tissues. Clinical implementation of fluorescence in situ hybridization (FISH) in cytogenetic laboratories allows for high-resolution analysis of recurrent structural chromosomal rearrangements specific to AML, especially in AML with normal karyotypes, which comprises approximately 33-50% of AML-positive specimens...
October 24, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28985529/multiplex-crispr-cas9-based-genome-editing-in-human-hematopoietic-stem-cells-models-clonal-hematopoiesis-and-myeloid-neoplasia
#6
Zuzana Tothova, John M Krill-Burger, Katerina D Popova, Catherine C Landers, Quinlan L Sievers, David Yudovich, Roger Belizaire, Jon C Aster, Elizabeth A Morgan, Aviad Tsherniak, Benjamin L Ebert
Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34(+) human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28958974/myeloid-neoplasia-and-lymphoblastic-lymphoma-with-eosinophilia-after-rai-a-case-report
#7
Mahmut Büyükşimşek, Semra Paydaş, Ali Oğul, Emine Bağır, Melek Ergin
BACKGROUND: Thyroid cancer is the most common endocrine cancers with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with genetic predisposition or radioactive iodine (RAI) used in the treatment. CASE REPORT: 65-year old male patient was operated for thyroid papillary cancer. Total thyroidectomy was performed. He received RAI two times. After six years he presented with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukemia/lymphoma, together...
September 29, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28917668/gut-microbe-mediated-suppression-of-inflammation-associated-colon-carcinogenesis-by-luminal-histamine-production
#8
Chunxu Gao, Bhanu Priya Ganesh, Zhongcheng Shi, Rajesh Rasik Shah, Robert Fultz, Angela Major, Susan Venable, Monica Lugo, Kathleen Hoch, Xiaowei Chen, Anthony Haag, Timothy C Wang, James Versalovic
Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b(+)Gr-1(+) immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc(+)Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc(-/-) mice...
October 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28804122/shp2-is-required-for-bcr-abl1-induced-hematologic-neoplasia
#9
S Gu, A Sayad, G Chan, W Yang, Z Lu, C Virtanen, R A Van Etten, B G Neel
BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph(+)) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation models for CML and BCR-ABL1(+) B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia...
August 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28765154/gemcitabine-induced-timp1-attenuates-therapy-response-and-promotes-tumor-growth-and-liver-metastasis-in-pancreatic-cancer
#10
Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y Lim, Ana L Gomes, Paul Kinchesh, Sean C Smart, W Gillies McKenna, Francesca M Buffa, Owen J Sansom, Ruth J Muschel, Eric O'Neill, Emmanouil Fokas
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in preclinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28725653/calr-positive-myeloproliferative-disorder-in-a-patient-with-ph-positive-chronic-myeloid-leukemia-in-durable-treatment-free-remission-a-case-report
#11
Irene Dogliotti, Carmen Fava, Anna Serra, Enrico Gottardi, Filomena Daraio, Francesca Carnuccio, Emilia Giugliano, Monica Bocchia, Giuseppe Saglio, Giovanna Rege-Cambrin
Current diagnostic criteria for Philadelphia-negative myeloproliferative neoplasia (MPN) have been redefined by the discovery of Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL) and calreticulin (CALR) genetic alterations. Only few cases of coexistence of CALR-mutated MPN and Philadelphia-positive chronic myeloid leukemia (CML) have been described so far. Here we report the case of a patient with CML diagnosed in 2001, treated with imatinib and pegylated interferon (IFN) frontline. She reached complete molecular remission (CMR) and discontinued imatinib, maintaining treatment free remission...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28680586/pulmonary-extra-medullary-hematopoiesis-and-pulmonary-hypertension-from-underlying-polycythemia-vera-a-case-series
#12
Inderjit Singh, Geoffrey Mikita, Daniel Green, Cristobal Risquez, Abraham Sanders
Myeloproliferative neoplasia (MPN)-associated pulmonary hypertension (PH) is included in group five of the most recent clinical classification of PH.(1) The MPNs are a heterogeneous group of disorders that includes disorders with primary expression of a myeloid phenotype and disorders characterized by expression of the Janus Kinase 2 (JAK2) mutation, p.V617F. The latter includes essential thrombocytosis, polycythemia vera, and idiopathic myelofibrosis.(2) Pulmonary extra-medullary hematopoiesis (EMH) refers to the presence of hematopoietic precursor cells in the lung...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28643018/heterogeneity-of-gata2-related-myeloid-neoplasms
#13
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...
August 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28637623/ddx41-related-myeloid-neoplasia
#14
REVIEW
Jaroslaw P Maciejewski, Richard A Padgett, Anna L Brown, Carsten Müller-Tidow
While early presentation of familial leukemia syndromes is typical, long disease anticipation may mask cases of familial traits in seemingly spontaneous disease. Germline mutations in DDX41 gene have been discovered in several leukemia families, as well as in mostly adult patients with seemingly spontaneous disease but having strong family histories of myeloid neoplasia. As with other familial genes, DDX41 mutation carriers can develop neoplasia through acquisition of another somatic mutation, thereby affecting both DDX41 alleles...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#15
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/28637618/recognition-of-familial-myeloid-neoplasia-in-adults
#16
REVIEW
Anna L Brown, Jane E Churpek, Luca Malcovati, Hartmut Döhner, Lucy A Godley
Hereditary hematologic malignancy (HM) syndromes are increasingly recognized as causative of adult hematopoietic cancers, and the advent of next-generation sequencing has accelerated the discovery of new syndromes based on dense clustering of these diseases in particular families. Updated classifications schemes for myeloid malignancies will now include recommendations for taking a family history on all patients diagnosed with hematopoietic malignancies and for genetic counseling and testing of appropriate individuals and families...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637617/introduction-genetic-syndromes-predisposing-to-myeloid-neoplasia
#17
EDITORIAL
Marcin W Wlodarski, Charlotte M Niemeyer
No abstract text is available yet for this article.
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28626217/irf8-regulates-the-progression-of-myeloproliferative-neoplasm-mpn-like-syndrome-via-mertk-signaling-in-zebrafish
#18
F Zhao, Y Shi, Y Huang, Y Zhan, L Zhou, Y Li, Y Wan, H Li, H Huang, H Ruan, L Luo, L Li
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8 mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28576876/targeting-chronic-myeloid-leukemia-stem-cells-with-the-hypoxia-inducible-factor-inhibitor-acriflavine
#19
Giulia Cheloni, Michele Tanturli, Ignazia Tusa, Ngoc Ho DeSouza, Yi Shan, Antonella Gozzini, Fréderic Mazurier, Elisabetta Rovida, Shaoguang Li, Persio Dello Sbarba
Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by expression of the constitutively active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable of targeting LSCs appears therefore of primary importance to aim at CML eradication...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#20
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
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