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Multiple myeloma ,leukemia

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https://www.readbyqxmd.com/read/27914102/examining-temporal-effects-on-cancer-risk-in-the-international-nuclear-workers-study-inworks
#1
Robert D Daniels, Stephen J Bertke, David B Richardson, Elisabeth Cardis, Michael Gillies, Jacqueline A O'Hagan, Richard Haylock, Dominique Laurier, Klervi Leuraud, Monika Moissonnier, Isabelle Thierry-Chef, Ausrele Kesminiene, Mary K Schubauer-Berigan
The paper continues the series of publications from the International Nuclear Workers Study cohort (INWORKS) that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure...
December 3, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#2
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#3
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#4
I J F Hofman, M Van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899805/circulating-tumour-dna-analysis-demonstrates-spatial-mutational-heterogeneity-that-coincides-with-disease-relapse-in-myeloma
#5
S Mithraprabhu, T Khong, M Ramachandran, A Chow, D Klarica, L Mai, S Walsh, D Broemeling, A Marziali, M Wiggin, J Hocking, A Kalff, B Durie, A Spencer
Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multi-focal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed [RR] and 15 newly diagnosed [ND] patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget™ Mutation Detection (OMD) platform...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#6
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27890933/preclinical-activity-of-cpi-0610-a-novel-small-molecule-bromodomain-and-extra-terminal-protein-inhibitor-in-the-therapy-of-multiple-myeloma
#7
K T Siu, J Ramachandran, A J Yee, H Eda, L Santo, C Panaroni, J A Mertz, R J Sims, M R Cooper, N Raje
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the anti-tumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing Phase I clinical testing, in multiple myeloma (MM)...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90-rasgrp1-and-hsp90-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#8
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here we show that trichostatin A, romidepsin, and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine, and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890927/the-ap-1-transcription-factor-junb-is-essential-for-multiple-myeloma-cell-proliferation-and-drug-resistance-in-the-bone-marrow-microenvironment
#9
F Fan, M H Bashari, E Morelli, G Tonon, S Malvestiti, S Vallet, M Jarahian, A Seckinger, D Hose, L Bakiri, C Sun, Y Hu, C R Ball, H Glimm, M Sattler, H Goldschmidt, E F Wagner, P Tassone, D Jaeger, K Podar
Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly due to the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27881873/induction-of-iron-excess-restricts-malignant-plasma-cells-expansion-and-potentiates-bortezomib-effect-in-models-of-multiple-myeloma
#10
J Bordini, S Galvan, M Ponzoni, M T S Bertilaccio, M Chesi, P L Bergsagel, C Camaschella, A Campanella
Leukemia accepted article preview online, 24 November 2016. doi:10.1038/leu.2016.346.
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#11
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#12
REVIEW
Alessandro Allegra, Vanessa Innao, Demetrio Gerace, Doriana Vaddinelli, Caterina Musolino
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors...
November 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27860411/secondary-primary-malignancies-during-the-lenalidomide-dexamethasone-regimen-in-relapsed-refractory-multiple-myeloma-patients
#13
Rouslan Kotchetkov, Esther Masih-Khan, Chia-Min Chu, Eshetu G Atenafu, Christine Chen, Vishal Kukreti, Suzanne Trudel, Rodger Tiedemann, Donna E Reece
Lenalidomide in combination with dexamethasone (Len-dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len-dex at our institution. The median follow-up time from diagnosis of MM was 73 months (10-234 months) and from initiation of Len-dex was 19 months (1-104 months)...
November 18, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27857131/epigenetic-silencing-of-mir-137-induces-drug-resistance-and-chromosomal-instability-by-targeting-aurka-in-multiple-myeloma
#14
Y Qin, S Zhang, S Deng, G An, X Qin, F Li, Y Xu, M Hao, Y Yang, W Zhou, H Chang, L Qiu
Multiple myeloma (MM) is the second most prevalent hematologic malignancy. Aberrant microRNAs (miRNAs) expression has been shown to be involved in the pathogenesis of MM. In this study, we further demonstrated that miR-137 was significantly downregulated in MM and negatively correlated with clinical prognosis. Moreover, we described the epigenetic regulation of miR-137 and its association with progression free survival in MM patients. Furthermore, overexpression of miR-137 in MM cell line (miR-137OE) increased its sensitivity to bortezomib and eprirubicin in vitro...
November 18, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#15
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27833979/multiple-myeloma-and-secondary-plasma-cell-leukemia
#16
Vitorino Modesto Dos Santos, Sandro Pinheiro Melim, Priscilla Souza de Faria, Viviane Vieira Passini, Mayza Lemes Duarte, Renata Athayde Casasanta
Plasma cell leukemia is very rare condition characterized by malignant proliferation of plasma cells in blood and bone marrow, which is aggressive and has a short survival even with conventional treatment. This ominous entity may be primary, or develops secondarily during the course of multiple myeloma. A 53-year-old Brazilian woman with multiple myeloma is described with bone marrow evaluation revealing 25% plasma cells. The quantification of plasma cell infiltration in bone marrow aspirate and immunohistochemistry study revealed consistent features of myeloma and plasma cell leukemia, and lambda light chain expression...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27822103/the-danish-national-multiple-myeloma-registry
#17
REVIEW
Peter Gimsing, Morten O Holmström, Tobias Wirenfelt Klausen, Niels Frost Andersen, Henrik Gregersen, Robert Schou Pedersen, Torben Plesner, Per Trøllund Pedersen, Mikael Frederiksen, Ulf Frølund, Carsten Helleberg, Annette Vangsted, Peter de Nully Brown, Niels Abildgaard
AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim is to support research. Patients are registered with their unique Danish personal identification number, and the combined use of DMMR, other Danish National registries, and the Danish National Cancer Biobank offers a unique platform for population-based translational research...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27819179/plasma-cell-leukemia-update-on-biology-and-therapy
#18
Roberto Mina, Mattia D'Agostino, Chiara Cerrato, Francesca Gay, Antonio Palumbo
Plasma cell leukemia (PCL) is a rare, but very aggressive, plasma cell dyscrasia, representing a distinct clinicopathological entity as compared to multiple myeloma (MM), with peculiar biological and clinical features. A hundred times rarer than MM, the disease course is characterized by short remissions and poor survival. PCL is defined by an increased percentage (>20%) and absolute number (>2 × 10(9)/l) of plasma cells in the peripheral blood. PCL is defined as 'primary' when peripheral plasmacytosis is detected at diagnosis, 'secondary' when leukemization occurs in a patient with preexisting MM...
November 6, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27795764/-primary-plasma-cell-leukemia-about-3-cases
#19
Mouhcine Miloudi, Nezha Messaoudi
Plasma cell leukemia is a rare hematologic malignancy defined by the presence of more than 20% of leukocyte count plasma cells or by a number of circulating plasma cells greater than 2 × 10(9)/L (2G/L). It may be primary in 60% of cases and it manifests itself immediately as a leukemia or as a secondary event, in 40% of cases, complicating a previously diagnosed multiple myeloma. Given the rarity of this condition, only a few cases have been reported in the literature. It is characterized by its aggressiveness and poor prognosis...
2016: Pan African Medical Journal
https://www.readbyqxmd.com/read/27787922/bone-health-in-patients-with-hematopoietic-disorders-of-bone-marrow-origin-systematic-review-and-meta-analysis
#20
Kieran Steer, Mariya Stavnichuk, Martin Morris, Svetlana V Komarova
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis...
October 27, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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