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https://www.readbyqxmd.com/read/28634317/the-role-of-frontline-autologous-stem-cell-transplantation-for-primary-plasma-cell-leukemia-a-retrospective-multicenter-study-kmm160
#1
Sung-Hoon Jung, Je-Jung Lee, Kihyun Kim, Cheolwon Suh, Dok Hyun Yoon, Chang-Ki Min, Sang Kyun Sohn, Chul Won Choi, Ho Sup Lee, Hyo Jung Kim, Ho-Jin Shin, Soo-Mee Bang, Sung-Soo Yoon, Seong Kyu Park, Ho-Young Yhim, Min Kyoung Kim, Jae-Cheol Jo, Yeung-Chul Mun, Jae Hoon Lee, Jin Seok Kim
Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28626216/therapeutic-effects-of-csf1r-blocking-antibodies-in-multiple-myeloma
#2
Q Wang, Y Lu, R Li, Y Jiang, Y Zheng, J Qian, E Bi, C Zhang, J Hou, S Wang, Q Yi
Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs) induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4(+) T cell response...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28620566/leukemia-cutis-associated-with-secondary-plasma-cell-leukemia
#3
Nicole C DeMartinis, Megan M Brown, Brian R Hinds, Philip R Cohen
Plasma cell leukemia is an uncommon, aggressive variant of leukemia that may occur de novo or in association with multiple myeloma. Leukemia cutis is the cutaneous manifestation of leukemia, and indicates an infiltration of the skin by malignant leukocytes or their precursors. Plasma cell leukemia cutis is a rare clinical presentation of leukemia. We present a man who developed plasma cell leukemia cutis in association with multiple myeloma. Cutaneous nodules developed on his arms and legs 50 days following an autologous stem cell transplant...
May 9, 2017: Curēus
https://www.readbyqxmd.com/read/28620163/natural-history-of-relapsed-myeloma-refractory-to-immunomodulatory-drugs-and-proteasome-inhibitors-a-multicenter-imwg-study
#4
S K Kumar, M A Dimopoulos, E Kastritis, E Terpos, H Nahi, H Goldschmidt, J Hillengass, X Leleu, M Beksac, M Alsina, A Oriol, M Cavo, E M Ocio, M V Mateos, E K O'Donnell, R Vij, H M Lokhorst, N W C J van de Donk, C Min, T Mark, I Turesson, M Hansson, H Ludwig, S Jagannath, M Delforge, C Kyriakou, P Hari, U Mellqvist, S Z Usmani, D Dytfeld, A Z Badros, P Moreau, K Kim, P R Otero, J H Lee, C Shustik, D Waller, W J Chng, S Ozaki, J-J Lee, J de la Rubia, H S Eom, L Rosinol, J J Lahuerta, A Sureda, J S Kim, B G M Durie
Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study...
May 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28612296/kinesin-5-blocker-monastrol-protects-against-bortezomib-induced-peripheral-neurotoxicity
#5
Ilja Bobylev, Dominik Peters, Maulik Vyas, Mohammed Barham, Ines Klein, Elke Pogge von Strandmann, Wolfram F Neiss, Helmar C Lehmann
Neurotoxicity is a relevant side effect of bortezomib treatment. Previous reports have shown that the development of peripheral neuropathy caused by anti-neoplastic agents may be a result of reduced axonal transport. Based on evidence from prior studies that the kinesin-5 inhibitor monastrol enhances axonal transport and improves neuronal regeneration, we focused on the neuroprotective role of monastrol during the chemotherapeutic treatment with bortezomib. Prolonged treatment of C57BL/6 mice with bortezomib induced a length-dependent small-fiber neuropathy with axonal atrophy and loss of sensory nerve fibers...
June 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28602141/cardiac-hematological-malignancies-typical-growth-patterns-imaging-features-and-clinical-outcome
#6
Peter Voigt, Susanne Wienbeck, Marc-André Weber, Noriko Oyama-Manabe, Maximilian Beimler, Stefan Schob, Thomas Kahn, Hans Jonas Meyer, Jan Frieso Randaxhe, Alexey Surov
Cardiac hematological malignancies (CHMs) are rare entities and comprise lymphoma, leukemic infiltration, and extramedullary manifestation of multiple myeloma. The aim of this work is to summarize typical growth patterns, imaging features, and outcome parameters of CHM. Overall, 12 cases from 4 centers were reviewed retrospectively together with 604 cases from the literature. Cardiac hematological malignancies were mainly represented by B-cell lymphoma (70.0%). Other entities were rarer. Almost half of the patients showed involvement of multiple cardiac structures...
January 1, 2017: Angiology
https://www.readbyqxmd.com/read/28601406/kidney-function-proteinuria-and-cancer-incidence-the%C3%A2-korean%C3%A2-heart-study
#7
Yejin Mok, Kunihiro Matsushita, Shoshana H Ballew, Yingying Sang, Keum Ji Jung, Sunmi Lee, Sun Ha Jee, Josef Coresh
BACKGROUND: Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort. STUDY DESIGN: A prospective cohort study. SETTING & PARTICIPANTS: 242,583 adults (30-74 years old) without a diagnosis of cancer at baseline in the Korean Heart Study, based on health checkups in 1996 to 2004 with follow-up until 2012...
June 7, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28588864/coexistence-of-chronic-lymphocytic-leukemia-and-multiple-myeloma-do-the-roots-of-these-entities-originate-from-the-same-place
#8
Alparslan Merdin, Jale Yıldız, Mehmet Sinan Dal, Merih Kızıl Çakar, Ali Hakan Kaya, Emre Tekgündüz, Fevzi Altuntaş
Multiple myeloma is a plasma cell disease, whereas CLL (Chronic Lymphocytic Leukemia) affects mature B-cell lymphocytes. Even though the coexistence of those two conditions is extremely rare, as both cell types differentiate from the same multipotent stem cells, the clinician should evaluate patients carefully not to misdiagnose such a concomitancy.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28588253/nucleotide-excision-repair-ner-is-a-potential-therapeutic-target-in-multiple-myeloma
#9
R Szalat, M K Samur, M Fulciniti, M Lopez, P Nanjappa, A Cleynen, K Wen, S Kumar, T Perrini, A S Calkins, E Reznichenko, D Chauhan, Y-T Tai, M Shammas, J-P Fermand, B Arnulf, H Avet-Loiseau, J-B Lazaro, N C Munshi
Nucleotide excision repair is active in multiple myeloma cells.Inhibition of NER increases sensitivity to alkylating agent.NER is a potential target for multiple myeloma treatment. Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents, therefore we here evaluate the role of nucleotide excision repair (NER) which is involved in the removal of bulky adducts and DNA crosslinks in MM...
June 7, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28584253/prediction-of-outcome-in-newly-diagnosed-myeloma-a-meta-analysis-of-the-molecular-profiles-of-1-905-trial-patients
#10
V Shah, A L Sherborne, B A Walker, D C Johnson, E M Boyle, S Ellis, D B Begum, P Z Proszek, J R Jones, C Pawlyn, S Savola, M W Jenner, M T Drayson, R G Owen, R S Houlston, D A Cairns, W M Gregory, G Cook, F E Davies, G H Jackson, G J Morgan, M F Kaiser
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28553616/the-oncolytic-virotherapy-era-in-cancer-management-prospects-of-applying-h-1-parvovirus-to-treat-blood-and-solid-cancers
#11
Assia L Angelova, Mathias Witzens-Harig, Angel S Galabov, Jean Rommelaere
Non-Hodgkin lymphoma (NHL) and leukemia are among the most common cancers worldwide. While the treatment of NHL/leukemia of B-cell origin has much progressed with the introduction of targeted therapies, few treatment standards have been established for T-NHL/leukemia. As presentation in both B- and T-NHL/leukemia patients is often aggressive and as prognosis for relapsed disease is especially dismal, this cancer entity poses major challenges and requires innovative therapeutic approaches. In clinical trials, oncolytic viruses (OVs) have been used against refractory multiple myeloma (MM)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28544116/incidence-characteristics-and-outcome-of-solitary-plasmacytoma-and-plasma-cell-leukemia-population-based-data-from-the-swedish-myeloma-register
#12
Hareth Nahi, Anna Genell, Göran Wålinder, Katarina Uttervall, Gunnar Juliusson, Karin Forsberg, Markus Hansson, Ronald Svensson, Olle Linder, Kristina Carlson, Bo Björkstrand, Sigurdur Y Kristinsson, Ulf Henrik Mellqvist, Cecilie Blimark, Ingemar Turesson
Solitary plasmacytoma (SP) and Plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP), (n=124) and extramedullary plasmacytoma (EMP), (n=67) have better overall survival (OS) than MM (n=3549)...
May 22, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#13
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl), an osteocyte-derived inhibitor of Wnt/β-catenin signaling, is elevated in MM patient sera and increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28525996/cancer-risks-in-a-population-based-study-of-70-570-agricultural-workers-results-from-the-canadian-census-health-and-environment-cohort-canchec
#14
Linda Kachuri, M Anne Harris, Jill S MacLeod, Michael Tjepkema, Paul A Peters, Paul A Demers
BACKGROUND: Agricultural workers may be exposed to potential carcinogens including pesticides, sensitizing agents and solar radiation. Previous studies indicate increased risks of hematopoietic cancers and decreased risks at other sites, possibly due to differences in lifestyle or risk behaviours. We present findings from CanCHEC (Canadian Census Health and Environment Cohort), the largest national population-based cohort of agricultural workers. METHODS: Statistics Canada created the cohort using deterministic and probabilistic linkage of the 1991 Canadian Long Form Census to National Cancer Registry records for 1992-2010...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28514772/risk-of-onset-of-hematological-malignancies-in-patients-infected-with-the-hepatitis-b-virus-results-from-a-large-scale-retrospective-cohort-study-in-china
#15
Xiaoyang Li, Yu Zheng, Hongming Zhu, Xiaojing Lin, Yunxiang Zhang, Yubing Zhao, Jiong Hu, Junmin Li
The hepatitis B virus (HBV) is a major global issue, because an increased risk of hepatocellular carcinoma among patients infected with HBV is well established. Recently, it has been suggested that HBV is associated with other human cancers. However, the association between HBV and the risk of onset of hematological malignancies remains controversial. The aim of this large-scale retrospective cohort study was to evaluate the association between HBV infection and hematological malignancies. A retrospective analysis of 86,115 newly admitted patients at Shanghai Ruijin Hospital was performed...
2017: Acta Haematologica
https://www.readbyqxmd.com/read/28508985/light-chain-fanconi-syndrome-in-a-patient-with-acute-myeloid-leukemia-and-monoclonal-gammopathy-of-undetermined-significance
#16
Daniel W Ross, Rimda Wanchoo, Adriana Guigova, Cristina Ghiuzeli, Steven L Allen, Kenar D Jhaveri
Proximal tubules are a target for paraproteinemic diseases. Cast nephropathy, light chain deposition diseases, and amyloidosis are frequently encountered in patients with multiple myeloma. Rarely, a subset of patients develop light chain Fanconi syndrome (LCFS). LCFS has been reported with multiple myeloma, monoclonal gammopathy of renal significance (MGRS), chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia and diffuse large B-cell lymphoma. No cases have been described with other hematologic malignancies...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28504647/identification-of-a-nucleoside-analog-active-against-adenosine-kinase-expressing-plasma-cell-malignancies
#17
Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J Barelli, Michelle A Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H Shoemaker, J David Warren, Olivier Elemento, Kenneth M Kaye, Ethel Cesarman
Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#18
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28490812/hdac3-regulates-dnmt1-expression-in-multiple-myeloma-therapeutic-implications
#19
T Harada, H Ohguchi, Y Grondin, S Kikuchi, M Sagawa, Y-T Tai, R Mazitschek, T Hideshima, K C Anderson
Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28487543/kdm6b-modulates-mapk-pathway-mediating-multiple-myeloma-cell-growth-and-survival
#20
H Ohguchi, T Harada, M Sagawa, S Kikuchi, Y-T Tai, P G Richardson, T Hideshima, K C Anderson
Recent studies have delineated cancer type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM); and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. TNFα or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting KDM6B is regulated by NF-κB signaling in MM cells. RNA-sequencing and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates these genes expression without affecting H3K27 methylation level...
May 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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