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Treatment Plasma cell leukemia

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https://www.readbyqxmd.com/read/28061985/multiple-myeloma-epidemiology-and-survival-a-unique-malignancy
#1
REVIEW
Dickran Kazandjian
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation followed by availability of novel treatments such as immunomodulatory drugs (ImIDs) and proteasome inhibitors (PIs) has transformed the natural history of the disease leading to longer survival times...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28056193/reduced-cd62l-expression-on-t-cells-and-increased-soluble-cd62l-levels-predict-molecular-response-to-tyrosine-kinase-inhibitor-therapy-in-early-chronic-phase-chronic-myelogenous-leukemia
#2
Sieghart Sopper, Satu Mustjoki, Deborah White, Timothy Hughes, Peter Valent, Andreas Burchert, Bjørn T Gjertsen, Günther Gastl, Matthias Baldauf, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Thomas Ernst, Thomas Schenk, Jeroen J W M Janssen, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#3
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death due to hemorrhage remains unacceptably common and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28049618/identification-of-a-melampomagnolide-b-analog-as-a-potential-lead-molecule-for-treatment-of-acute-myelogenous-leukemia
#4
Zaineb A F Albayati, Venumadhav Janganati, Zheng Chen, Jessica Ponder, Philip J Breen, Craig T Jordan, Peter A Crooks
A series of carbamate derivatives of the antileukemic sesquiterpene melampomagnolide B (MMB) has been synthesized utilizing a 1,2,4-triazole carbamate conjugate of MMB as an intermediate synthon. Five imidazole- and benzimidazole-carbamate analogs of MMB (8a-8e) were prepared and evaluated for anti-leukemic activity against cultured M9 ENL1 AML cells. All the analogs exhibited improved anti-leukemic activity (EC50=0.90-3.93μM) when compared to parthenolide and the parent sesquiterpene, MMB (EC50=7.0μM and 15...
December 26, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28043150/histone-deacetylase-inhibitors-in-plasma-cell-leukemia-treatment-effect-of-bone-marrow-microenvironment
#5
I Burianova, K Kuzelova, O Mitrovsky, I Spicka, P StOckbauer, M Zackova
In the presented study we analysed the effect of histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on human plasma cell leukemia (PCL) cell line UHKT-944 in the presence of bone marrow microenvironment (BMM). For the analysis, the cells were cultured alone, with bone marrow stromal cells (BMSCs), with extracellular matrix (ECM) components or with interleukin-6, and treated with varied concentrations of SAHA and VPA for 24/48 hours. To study the effect of HDACi, we investigated cell proliferation, apoptosis, cell cycle and changes in selected signalling pathways...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28038447/proteome-alterations-associated-with-transformation-of-multiple-myeloma-to-secondary-plasma-cell-leukemia
#6
Alexey Zatula, Aida Dikic, Celine Mulder, Animesh Sharma, Cathrine B Vågbø, Mirta M L Sousa, Anders Waage, Geir Slupphaug
Plasma cell leukemia is a rare and aggressive plasma cell neoplasm that may either originate de novo (primary PCL) or by leukemic transformation of multiple myeloma (MM) to secondary PCL (sPCL). The prognosis of sPCL is very poor, and currently no standard treatment is available due to lack of prospective clinical studies. In an attempt to elucidate factors contributing to transformation, we have performed super-SILAC quantitative proteome profiling of malignant plasma cells collected from the same patient at both the MM and sPCL stages of the disease...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#7
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28025583/a-novel-bcma-cd3-bi-specific-t-cell-engager-for-the-treatment-of-multiple-myeloma-induces-selective-lysis-in-vitro-and-in-vivo
#8
S Hipp, Y-T Tai, D Blanset, P Deegen, J Wahl, O Thomas, B Rattel, P J Adam, K Anderson, M Friedrich
B cell maturation antigen (BCMA) is a highly plasma cell selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T cell redirecting therapies. We developed a bispecific T cell engager (BiTE(®)) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T cell proliferation; whereas BCMA-negative cells were not affected...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27998645/thrombotic-microangiopathy-associated-with-monoclonal-gammopathy
#9
Aishwarya Ravindran, Ronald S Go, Fernando C Fervenza, Sanjeev Sethi
Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13...
December 17, 2016: Kidney International
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#10
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/27859216/cooperation-of-mll-af10-om-lz-with-ptpn11-activating-mutation-induced-monocytic-leukemia-with-a-shorter-latency-in-a-mouse-bone-marrow-transplantation-model
#11
Jen-Fen Fu, Sung-Tzu Liang, Ying-Jung Huang, Kung-Hao Liang, Tzung-Hai Yen, Der-Cherng Liang, Lee-Yung Shih
PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11(G503A) . To study the impact of PTPN11(G503A) cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared to the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11(wt) , the cells harboring PTPN11(G503A) were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#12
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27853634/dynamic-alterations-of-bone-marrow-cytokine-landscape-of-myelodysplastic-syndromes-patients-treated-with-5-azacytidine
#13
Alena Moudra, Sona Hubackova, Veronika Machalova, Marketa Vancurova, Jiri Bartek, Milan Reinis, Zdenek Hodny, Anna Jonasova
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis frequently progressing into acute myeloid leukemia (AML), with emerging evidence implicating aberrant bone marrow (BM) microenvironment and inflammation-related changes. 5-azacytidine (5-AC) represents standard MDS treatment. Besides inhibiting DNA/RNA methylation, 5-AC has been shown to induce DNA damage and apoptosis in vitro. To provide insights into in vivo effects, we assessed the proinflammatory cytokines alterations during MDS progression, cytokine changes after 5-AC, and contribution of inflammatory comorbidities to the cytokine changes in MDS patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27833979/multiple-myeloma-and-secondary-plasma-cell-leukemia
#14
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/27825464/prognostic-factors-and-indications-for-treatment-of-waldenstr%C3%A3-m-s-macroglobulinemia
#15
REVIEW
Robert A Kyle, Stephen M Ansell, Prashant Kapoor
Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5(-), CD10(-), CD19(+), CD20(+) and CD23(-). Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa-associated lymphoid tissue (MALT) lymphoma must be excluded...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27822103/the-danish-national-multiple-myeloma-registry
#16
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
#17
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/27802968/calreticulin-exposure-by-malignant-blasts-correlates-with-robust-anticancer-immunity-and-improved-clinical-outcome-in-aml-patients
#18
Jitka Fucikova, Iva Truxova, Michal Hensler, Etienne Becht, Lenka Kasikova, Irena Moserova, Sarka Vosahlikova, Jana Klouckova, Sarah E Church, Isabelle Cremer, Oliver Kepp, Guido Kroemer, Lorenzo Galluzzi, Cyril Salek, Radek Spisek
Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called "damage-associated molecular patterns," DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from patients with acute myeloid leukemia (AML) exposed multiple DAMPs, including calreticulin (CRT), heat-shock protein 70 (HSP70), and HSP90 on their plasma membrane irrespective of treatment...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27797340/sorting-protein-vps33b-regulates-exosomal-autocrine-signaling-to-mediate-hematopoiesis-and-leukemogenesis
#19
Hao Gu, Chiqi Chen, Xiaoxin Hao, Conghui Wang, Xiaocui Zhang, Zhen Li, Hongfang Shao, Hongxiang Zeng, Zhuo Yu, Li Xie, Fangzhen Xia, Feifei Zhang, Xiaoye Liu, Yaping Zhang, Haishan Jiang, Jun Zhu, Jiangbo Wan, Chun Wang, Wei Weng, Jingjing Xie, Minfang Tao, Cheng Cheng Zhang, Junling Liu, Guo-Qiang Chen, Junke Zheng
Certain secretory proteins are known to be critical for maintaining the stemness of stem cells through autocrine signaling. However, the processes underlying the biogenesis, maturation, and secretion of these proteins remain largely unknown. Here we demonstrate that many secretory proteins produced by hematopoietic stem cells (HSCs) undergo exosomal maturation and release that is controlled by vacuolar protein sorting protein 33b (VPS33B). Deletion of VPS33B in either mouse or human HSCs resulted in impaired exosome maturation and secretion as well as loss of stemness...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27776282/nanoassemblies-from-amphiphilic-cytarabine-prodrug-for-leukemia-targeted-therapy
#20
Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
February 1, 2017: Journal of Colloid and Interface Science
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