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Treatment Plasma cell leukemia

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https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#1
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28920465/fish-oil-derived-eicosapentaenoic-acid-decreases-survivin-expression-and-induces-wt-p53-accumulation-with-caspase-3-activation-in-acute-lymphoblastic-leukemia-cells
#2
M R Sam, M Esmaeillou, S Sam, M A Shokrgozar
BACKGROUND: Defects in modulating wild-type (wt) p53 and survivin are associated with a resistant disease in acute lymphoblastic leukemia (ALL). Yet, no wt-p53 and survivin modulating drugs have been approved for clinical application in ALL. Here, we investigated if in vitro eicosapentaenoic acid (EPA) concentrations equal to human plasma levels are able to target wt-p53 and survivin. METHODS: Wt-p53 Molt-4 cells (ALL cell line) were treated with 50, 100, 150, and 200 µM of EPA after which cell number, viability, proliferation rate, survivin expression, wt-p53 accumulation, caspase-3 activation, and apoptosis were evaluated...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28919785/biomarker-analysis-and-clinical-relevance-of-tk1-on-the-cell-membrane-of-burkitt-s-lymphoma-and-acute-lymphoblastic-leukemia
#3
Evita G Weagel, Wei Meng, Michelle H Townsend, Edwin J Velazquez, Rachel A Brog, Michael W Boyer, K Scott Weber, Richard A Robison, Kim L O'Neill
TK1 is an enzyme involved in DNA synthesis and repair. TK1 is usually found elevated in cancer patients' serum, which makes it a useful tumor proliferation biomarker that strongly correlates with cancer stage, metastatic capabilities, and recurrence risk. In this study, we show that TK1 is upregulated and localizes on the plasma membrane of Burkitt's lymphoma, acute promyelocytic leukemia, T cell leukemia, and acute lymphoblastic leukemia (ALL). Using flow cytometry, we confirmed that TK1 localizes on the surface of Raji, HL60, and Jurkat cell lines and on ALL clinical samples...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28884441/inhibition-of-retroviral-gag-assembly-by-non-silencing-mirnas-promotes-autophagic-viral-degradation
#4
Na Qu, Zhao Ma, Mengrao Zhang, Muaz N Rushdi, Christopher J Krueger, Antony K Chen
We recently reported an unconventional mechanism by which miRNAs inhibit HIV-1 viral production. This occurs when miRNAs bind nonspecifically to the viral structural protein Gag, interfering with viral RNA-mediated Gag assembly at the plasma membrane. Consequently, misassembled viral complexes are redirected into the endocytic pathway where they are delivered to lysosomes for degradation. In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific...
September 7, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28871936/xanthoma-like-skin-changes-in-an-elderly-woman-with-a-normal-lipid-profile
#5
Piotr Nockowski, Zdzisław Woźniak, Adam Reich, Joanna Maj
Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28864289/phase-1-clinical-trial-of-adoptive-immunotherapy-using-off-the-shelf-activated-natural-killer-cells-in-patients-with-refractory-and-relapsed-acute-myeloid-leukemia
#6
Michael Boyiadzis, Mounzer Agha, Robert L Redner, Alison Sehgal, Annie Im, Jing-Zhou Hou, Rafic Farah, Kathleen A Dorritie, Anastasios Raptis, Seah H Lim, Hong Wang, Natalia Lapteva, Zhuyong Mei, Lisa H Butterfield, Cliona M Rooney, Theresa L Whiteside
BACKGROUND AIMS: Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated. METHODS: Two cell-dose levels (1 × 10(9) cells/m(2) and 3 × 10(9) cells/m(2)) were used...
August 29, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28830598/do-immunoglobulin-g-and-immunoglobulin-e-anti-l-asparaginase-antibodies-have-distinct-implications-in-children-with-acute-lymphoblastic-leukemia-a-cross-sectional-study
#7
Gabriela Galindo-Rodríguez, José C Jaime-Pérez, Mario C Salinas-Carmona, Sandra N González-Díaz, Ángeles Castro-Corona, Raúl Cavazos-González, Humberto Treviño-Villarreal, Alberto C Heredia-Salazar, David Gómez-Almaguer
BACKGROUND: l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. METHODS: Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied...
July 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28760306/high-risk-multiple-myeloma-definition-and-management
#8
REVIEW
Nisha S Joseph, Silvia Gentili, Jonathan L Kaufman, Sagar Lonial, Ajay K Nooka
The prognosis of patients with multiple myeloma has significantly improved after the introduction of novel concepts of immunomodulation and proteasome inhibition in myeloma therapies. In conjunction with the use of high-dose therapy and autologous stem cell transplantation, these newer antimyeloma agents facilitated the augmentation of deeper responses and as a result, enhanced survival outcomes. Despite mounting clinical evidence that novel therapies may mitigate the poor prognostic impact of some predictors historically considered "harbingers of doom" in myeloma such as t(4;14), the benefit of these advances is less evident in patients who present with genetically defined high-risk features such as presence of chromosomal abnormalities del17p, t(14;16), or t(14;20), or among patients presenting with plasma cell leukemia...
July 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28744022/granulocyte-colony-stimulating-factor-gcsf-fused-with-fc-domain-produced-from-e-coli-is-less-effective-than-polyethylene-glycol-conjugated-gcsf
#9
Bich Hang Do, Hyo Jeong Kang, Jung-A Song, Minh Tan Nguyen, Sangsu Park, Jiwon Yoo, Anh Ngoc Nguyen, Grace G Kwon, Jaepyeong Jang, Mihee Jang, Sunju Lee, Seoungjun So, Seongrak Sim, Kyung Jin Lee, Mark J Osborn, Han Choe
Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28711674/hplc-hg-afs-determination-of-arsenic-species-in-acute-promyelocytic-leukemia-apl-plasma-and-blood-cells
#10
Meihua Guo, Wenjing Wang, Xin Hai, Jin Zhou
Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO3H2O2 and analyzed by HG-AFS...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28702160/bk-virus-associated-hemorrhagic-cystitis-in-patients-with-allogeneic-hematopoietic-cell-transplantation-report-of-three-cases
#11
Duygu Mert, Hikmetullah Batgi, Alparslan Merdin, Sabahat Çeken, Mehmet Sinan Dal, Emre Tekgündüz, Fevzi Altuntaş, Mustafa Ertek
BK viras is a human polyoma viras. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28674892/surface-profiling-of-extracellular-vesicles-from-plasma-or-ascites-fluid-using-dotscan-antibody-microarrays
#12
Larissa Belov, Susannah Hallal, Kieran Matic, Jerry Zhou, Sandra Wissmueller, Nuzhat Ahmed, Sumaiya Tanjil, Stephen P Mulligan, O Giles Best, Richard J Simpson, Richard I Christopherson
DotScan antibody microarrays were initially developed for the extensive surface profiling of live leukemia and lymphoma cells. DotScan's diagnostic capability was validated with an extensive clinical trial using mononuclear cells from the blood or bone marrow of leukemia or lymphoma patients. DotScan has also been used for the profiling of surface proteins on peripheral blood mononuclear cells (PBMC) from patients with HIV, liver disease, and stable and progressive B-cell chronic lymphocytic leukemia (CLL)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28668490/co-infections-by-double-stranded-dna-viruses-after-ex-vivo-t-cell-depleted-cd34-selected-hematopoietic-cell-transplantation
#13
Yao-Ting Huang, Seong Jin Kim, Yeon Joo Lee, Daniel Burack, Paige Nichols, Molly Maloy, Miguel-Angel Perales, Sergio A Giralt, Ann A Jakubowski, Genovefa A Papanicolaou
Recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) are at risk of infection by double-stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV). Healthcare utilization in the first 6 months post-HCT was compared between patients with dsDNA viremia versus no viremia...
June 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#14
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28634317/the-role-of-frontline-autologous-stem-cell-transplantation-for-primary-plasma-cell-leukemia-a-retrospective-multicenter-study-kmm160
#15
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/28620566/leukemia-cutis-associated-with-secondary-plasma-cell-leukemia
#16
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/28619847/targeted-activation-of-the-shp-1-pp2a-signaling-axis-elicits-apoptosis-of-chronic-lymphocytic-leukemia-cells
#17
Elena Tibaldi, Mario Angelo Pagano, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Valeria Pavan, Luciana Bordin, Andrea Visentin, Francesca Zonta, Gianpietro Semenzato, Anna Maria Brunati, Livio Trentin
Lyn, a member of the Src family of kinases, is a key factor in the dysregulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and serine/threonine phosphatase 2A, eventually triggering apoptosis...
August 2017: Haematologica
https://www.readbyqxmd.com/read/28599273/targeting-bcr-abl-stem-progenitor-cells-and-bcr-abl-t315i-mutant-cells-by-effective-inhibition-of-the-bcr-abl-tyr177-grb2-complex
#18
Min Chen, Ali G Turhan, Hongxia Ding, Qingcong Lin, Kun Meng, Xiaoyan Jiang
Treatment of BCR-ABL+ human leukemia has been significantly improved by ABL tyrosine kinase inhibitors (TKIs), but they are not curative for most patients and relapses are frequently associated with BCR-ABL mutations, warranting new targets for improved treatments. We have now demonstrated that protein expression of human estrogen receptor alpha 36 (ERα36), an alternative splicing variant of human estrogen receptor alpha 66 (ERα66), is highly increased in TKI-insensitive CD34+ chronic myeloid leukemia (CML) cells and BCR-ABL-T315I mutant cells, and is abnormally localized in plasma membrane and cytoplasm...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596939/undifferentiated-pleomorphic-sarcoma-and-the-importance-of-considering-the-oncogenic-and-immune-suppressant-role-of-the-human-t-cell-lymphotropic-virus-type-1-a-case-report
#19
Sergio Lupo, Carolina Berini, Camila Cánepa, Eduardo Santini Araujo, Mirna Biglione
INTRODUCTION: Soft-tissue sarcomas account for 0.7% of all malignant tumors, with an incidence rate of 3 per 100,000 persons/year. The undifferentiated pleomorphic sarcoma (UPS) with giant cells, a high grade tumor of soft tissue, is very unusual, especially in young adults before the age of 40. Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus, classified as group 1 human carcinogens by The International Agency for Research on Cancer, that causes an aggressive malignancy known as adult T-cell lymphoma/leukemia and a progressive chronic inflammatory neurological disease named HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28562380/pharmacokinetics-of-venetoclax-in-patients-with-17p-deletion-chronic-lymphocytic-leukemia
#20
Ahmed Hamed Salem, Martin Dunbar, Suresh K Agarwal
Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal...
September 2017: Anti-cancer Drugs
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