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https://www.readbyqxmd.com/read/28725989/imatinib-in-myeloid-lymphoid-neoplasms-with-eosinophilia-and-rearrangement-of-pdgfrb-in-chronic-or-blast-phase
#1
Mohamad Jawhar, Nicole Naumann, Juliana Schwaab, Herrad Baurmann, Jochen Casper, Tu-Anh Dang, Lutz Dietze, Konstanze Döhner, Annette Hänel, Bernd Lathan, Hartmut Link, Sina Lotfi, Ole Maywald, Stephan Mielke, Lothar Müller, Uwe Platzbecker, Otto Prümmer, Henrike Thomssen, Karin Töpelt, Jens Panse, Tom Vieler, Wolf-Karsten Hofmann, Torsten Haferlach, Claudia Haferlach, Alice Fabarius, Andreas Hochhaus, Nicholas C P Cross, Andreas Reiter, Georgia Metzgeroth
We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10(9)/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively...
July 19, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28724539/racial-and-ethnic-disparities-in-hematologic-malignancies
#2
Kedar Kirtane, Stephanie J Lee
Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies...
July 19, 2017: Blood
https://www.readbyqxmd.com/read/28722833/targeted-next-generation-sequencing-using-a-multigene-panel-in-myeloid-neoplasms-implementation-in-clinical-diagnostics
#3
B Maes, J Willemse, A Broekmans, R Smets, B Cruys, N Put, V Madoe, M Janssen, O Soepenberg, G Bries, I Vrelust, R Achten, K Van Pelt, K Buvé, K Theunissen, V Peeters, G Froyen
INTRODUCTION: Detection of mutations in patients with myeloid neoplasms (MNs) has shown great potential for diagnostic and prognostic purposes. Next-generation sequencing (NGS) is currently implemented for the diagnostic profiling of the four major MN subgroups. METHODS: First, we validated the targeted NGS approach using the TruSight Myeloid panel. Next, we screened 287 patients with a clinical suspicion of MN and 61 follow-up patients with documented MN. RESULTS: Validation of the NGS workflow resulted in maximal precision, accuracy, sensitivity, and specificity for gene variants with an allele frequency of at least 5% and a minimal read depth of 300...
July 19, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28718071/cancer-survival-in-adult-patients-in-spain-results-from-nine-population-based-cancer-registries
#4
M D Chirlaque, D Salmerón, J Galceran, A Ameijide, A Mateos, A Torrella, R Jiménez, N Larrañaga, R Marcos-Gragera, E Ardanaz, M Sant, P Minicozzi, C Navarro, M J Sánchez
INTRODUCTION: With the aim of providing cancer control indicators, this work presents cancer survival in adult (≥15 years) patients in Spain diagnosed during the period 2000-2007 from Spanish cancer registries participating in the EUROCARE project. METHODS: Cancer cases from nine Spanish population-based cancer registries were included and analysed as a whole. All primary malignant neoplasms diagnosed in adult patients were eligible for the analysis. Cancer patients were followed until 31 December 2008...
July 17, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#5
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28689173/current-understanding-and-management-of-pulmonary-langerhans-cell-histiocytosis
#6
Robert Vassallo, Sergio Harari, Abdellatif Tazi
Pulmonary Langerhans cell histiocytosis (PLCH) is a diffuse lung disease that usually affects young adult smokers. PLCH affects different lung compartments; bronchiolar, interstitial and pulmonary vascular dysfunction may coexist to varying extents, resulting in diverse phenotypes. Analyses of PLCH tissues have identified activating mutations of specific mitogen-activated protein kinases (BRAF(V600E) and others). The current consensus is that PLCH represents a myeloid neoplasm with inflammatory properties: the myeloid tumour cells exhibit surface CD1a expression and up to 50% of the cells harbour activating BRAF or other MAPK mutations...
July 8, 2017: Thorax
https://www.readbyqxmd.com/read/28685257/budd-chiari-syndrome-hepatic-venous-outflow-tract-obstruction
#7
REVIEW
Dominique-Charles Valla
BACKGROUND: Budd-Chiari syndrome (BCS) is a rare disease characterized by hepatic venous outflow tract obstruction (HVOTO). METHODS: Recent literature has been analyzed for this narrative review. RESULTS: Primary BCS/HVOTO is a result of thrombosis. The same patient often has multiple risk factors for venous thrombosis and most have at least one. Presentation and etiology may differ between Western and certain Eastern countries. Myeloproliferative neoplasms are present in 40% of patients and are usually associated with the V617F-JAK2 mutation in myeloid cells, in particular peripheral blood granulocytes...
July 6, 2017: Hepatology International
https://www.readbyqxmd.com/read/28679734/high-prevalence-of-myeloid-neoplasms-in-adults-with-non-langerhans-cell-histiocytosis
#8
Matthias Papo, Eli L Diamond, Fleur Cohen-Aubart, Jean-François Emile, Damien Roos-Weil, Nishant Gupta, Benjamin H Durham, Neval Ozkaya, Ahmet Dogan, Gary A Ulaner, Raajit Rampal, Jean-Emmanuel Kahn, Thomas Sené, Frédéric Charlotte, Baptiste Hervier, Caroline Besnard, Olivier A Bernard, Catherine Settegrana, Nathalie Droin, Zofia Hélias-Rodzewicz, Zahir Amoura, Omar Abdel-Wahab, Julien Haroche
Erdheim-Chester Disease (ECD) is a rare non-Langerhans Cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAP kinase signaling. Due to the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans Cell Histiocytosis (so-called Mixed Histiocytosis (MH)), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms amongst patients with ECD and MH...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28676493/identifying-large-indels-in-targeted-next-generation-sequencing-assays-for-myeloid-neoplasms-a-cautionary-tale-of-the-zrsr1-pseudogene
#9
Isaac Ks Ng, Christopher Ng, Jia Jin Low, Lily Chiu, Elaine Seah, Chin Hin Ng, Wee-Joo Chng, Benedict Yan, Kenneth Hk Ban
Targeted next generation sequencing platforms have been increasingly utilised for identification of novel mutations in myeloid neoplasms, such as acute myeloid leukaemia (AML), and hold great promise for use in routine clinical diagnostics. In this study, we evaluated the utility of an open source variant caller in detecting large indels in a targeted sequencing of AML samples. While we found that this bioinformatics pipeline has the potential to accurately capture large indels (>20 bp) in patient samples, we highlighted the pitfall of a confounding ZRSR1 pseudogene that led to an erroneous ZRSR2 variant call...
July 4, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28667884/exome-sequencing-reveals-dnmt3a-and-asxl1-variants-associate-with-progression-of-chronic-myeloid-leukemia-after-tyrosine-kinase-inhibitor-therapy
#10
TaeHyung Kim, Marc S Tyndel, Zhaolei Zhang, Jaesook Ahn, Seunghyun Choi, Michael Szardenings, Jeffrey H Lipton, Hyeoung-Joon Kim, Dennis Kim Dong Hwan
OBJECTIVE: The development of tyrosine kinase inhibitors (TKIs) has significantly improved the treatment of chronic myeloid leukemia (CML). However, approximately one third of patients are resistant to TKI and/or progress to advanced disease stages. TKI therapy failure has a well-known association with ABL1 kinase domain (KD) mutations, but only around half of TKI non-responders have detectable ABL1 KD mutations. METHOD: We attempt to identify genetic markers associated with TKI therapy failure in 13 patients (5 resistant, 8 progressed) without ABL1 KD mutations using whole-exome sequencing...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28666496/atypical-chronic-myeloid-leukemia-bcr-abl1-negative-in-a-5-month-baby-arare-presentation
#11
Nazish Saqlain, Nisar Ahmed
Atypical chronic myeloid leukemia (aCML) is a neoplasm with poor prognosis, characterized by myeloid hyperplasia, dysmyelopoiesis and absence of BCR-ABL1 gene. Clinically, the disease course may be similar to chronic myeloid leukemia (CML), BCR-ABL1 positive. It presents in seventh to eighth decade of life with few cases of paediatric aCML being reported. Here, we report a case of aCMLin a 5-month baby who presented with massive splenomegaly. The diagnosis was in accordance with the WHO criteria established in 2008...
November 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28661409/cytogenetic-characterization-of-myeloid-neoplasms-with-t-2-3-p13-25-q25-29-an-analysis-of-60-cases
#12
Alexis V Dowiak, Carlos A Tirado
Chromosomal translocations involving the short arm of chromosome 2 (p13-25) and the distal part of the long arm of chromosome 3 (q25-29) are rare and still poorly studied to date. These abnormalities are common in myeloid neoplasms and are associated with a poor prognosis. Chromosomal abnormalities within the involved range of bands may contribute to the ectopic expression or formation of fusion genes involving the EVI1 gene, but the exact mechanism by which EVI1 affects leukemogenesis remains unclear. Herein, we report an analysis of 60 patient cases presenting various myeloid malignancies with t(2;3)(p13-25;q25-29) compiled from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28654364/practical-implications-of-the-2016-revision-of-the-world-health-organization-classification-of-lymphoid-and-myeloid-neoplasms-and-acute-leukemia
#13
John P Leonard, Peter Martin, Gail J Roboz
A major revision of the WHO classification of lymphoid and myeloid neoplasms and acute leukemia was released in 2016. A key motivation for this update was to include new information available since the 2008 version with clinical relevance for the diagnosis, prognosis, and therapy of patients. With > 100 entities described, it is important for the clinician to understand features that may be important in daily practice, whereas researchers need to incorporate the new classification scheme into study development and analysis...
June 27, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28648895/nuclear-factor-erythroid-2-regulates-human-hsc-self-renewal-and-t-cell-differentiation-by-preventing-notch1-activation
#14
Alessandro Di Tullio, Diana Passaro, Kevin Rouault-Pierre, Sukhveer Purewal, Dominique Bonnet
Nuclear factor erythroid-derived 2 (NF-E2) has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs) not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG) mice...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28643018/heterogeneity-of-gata2-related-myeloid-neoplasms
#15
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/28642604/turning-the-tide-in-myelodysplastic-myeloproliferative-neoplasms
#16
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/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#17
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28641661/-clinical-and-pathologic-features-of-myeloid-sarcoma
#18
Ya-Jun Jiang, Hong-Xia Wang, Wan-Chuan Zhuang, Hao Chen, Chang Zhang, Xiu-Mei Li, Gui-Hua Zhu, Yao He
OBJECTIVE: To explore the clinicopathologic features, differential diagnosis and therapy of myeloid sarcoma. METHODS: The clinical data including clinical manifestations, laboratorial tests, histopathologicical examination, immunohistochemistry and clinical prognosis of 10 patients with myeloid sarcoma were analyzed retrospectively. Among 10 patients, 5 male and 5 female, aged 23 to 71 years old (median = 36 years). RESULTS: 2 cases of myeloid sarcoma were secondary from chronic myeloid leukemia, and 1 cases of myeloid sarcoma occurred after the allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia, and the others lacked the anamnesis of malignancies...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#19
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#20
REVIEW
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
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