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https://www.readbyqxmd.com/read/29149251/parental-age-and-risk-of-lymphoid-neoplasms
#1
Gunnar Larfors, Ingrid Glimelius, Sandra Eloranta, Karin E Smedby
High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29148541/integrated-genomic-analysis-identifies-deregulated-jak-stat-myc-biosynthesis-axis-in-aggressive-nk-cell-leukemia
#2
Liang Huang, Dan Liu, Na Wang, Shaoping Ling, Yuting Tang, Jun Wu, Lingtong Hao, Hui Luo, Xuelian Hu, Lingshuang Sheng, Lijun Zhu, Di Wang, Yi Luo, Zhen Shang, Min Xiao, Xia Mao, Kuangguo Zhou, Lihua Cao, Lili Dong, Xinchang Zheng, Pinpin Sui, Jianlin He, Shanlan Mo, Jin Yan, Qilin Ao, Lugui Qiu, Hongsheng Zhou, Qifa Liu, Hongyu Zhang, Jianyong Li, Jie Jin, Li Fu, Weili Zhao, Jieping Chen, Xin Du, Guoliang Qing, Hudan Liu, Xin Liu, Gang Huang, Ding Ma, Jianfeng Zhou, Qian-Fei Wang
Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm that is more prevalent among people from Asia and Central and South America. Patients usually die within days to months, even after receiving prompt therapeutic management. Here we performed the first comprehensive study of ANKL by integrating whole genome, transcriptome and targeted sequencing, cytokine array as well as functional assays. Mutations in the JAK-STAT pathway were identified in 48% (14/29) of ANKL patients, while the extracellular STAT3 stimulator IL10 was elevated by an average of 56-fold (P < 0...
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29146910/an-unexpected-protein-interaction-promotes-drug-resistance-in-leukemia
#3
Aaron Pitre, Yubin Ge, Wenwei Lin, Yao Wang, Yu Fukuda, Jamshid Temirov, Aaron H Phillips, Jennifer L Peters, Yiping Fan, Jing Ma, Amanda Nourse, Chandrima Sinha, Hai Lin, Richard Kriwacki, James R Downing, Tanja A Gruber, Victoria E Centonze, Anjaparavanda P Naren, Taosheng Chen, John D Schuetz
The overall survival of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related therapeutic targets remains a major goal for this disease. Here we show that expression of MPP1, a PDZ-domain-containing protein, highly correlated with ABCC4 in AML, is associated with worse overall survival in AML. Murine hematopoietic progenitor cells overexpressing MPP1 acquired the ability to serially replate in methylcellulose culture, a property crucially dependent upon ABCC4. The highly conserved PDZ-binding motif of ABCC4 is required for ABCC4 and MPP1 to form a protein complex, which increased ABCC4 membrane localization and retention, to enhance drug resistance...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29140406/smad3-stat3-crosstalk-in-pathophysiological-contexts
#4
Yuka Itoh, Masao Saitoh, Keiji Miyazawa
Smad3 and STAT3 are intracellular molecules that transmit signals from plasma membrane receptors to the nucleus. Smad3 operates downstream of growth/differentiation factors that utilize activin receptor-like kinase (ALK)-4, 5, or 7, such as transforming growth factor-β (TGF-β), activin, and myostatin. STAT3 principally functions downstream of cytokines that exert their effects via gp130 and Janus family kinases, including interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M. Accumulating evidence indicates that Smad3 and STAT3 engage in crosstalk in a highly context-dependent fashion, cooperating in some conditions while acting antagonistically each other in others...
November 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29136959/alterations-of-biomechanics-in-cancer-and-normal-cells-induced-by-doxorubicin
#5
Kaja Fraczkowska, Marcin Bacia, Magda Przybyło, Dominik Drabik, Aleksandra Kaczorowska, Justyna Rybka, Ewa Stefanko, Slawomir Drobczynski, Jan Masajada, Halina Podbielska, Tomasz Wrobel, Marta Kopaczynska
Mechanical properties of biological structures play an important role in regulating cellular activities and are critical for understanding metabolic processes in cancerous cells and the effects of drugs. For some cancers, such as acute myeloid leukaemia, chemotherapy is one of preferential methods. However, due to the lack of selectivity to cancer cells, cytostatic agents cause toxicity to normal tissues. Here, we study the effect of doxorubicin (DOX) on the mechanical properties of DNA molecules, leukemic blast cells and erythrocytes, using optical tweezers...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29119293/asparaginase-erwinia-chrysanthemi-effectively-depletes-plasma-glutamine-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia
#6
Ashkan Emadi, Jennie Y Law, Erin T Strovel, Rena G Lapidus, Linda J B Jeng, Myounghee Lee, Miriam G Blitzer, Brandon A Carter-Cooper, Danielle Sewell, Isabella Van Der Merwe, Sunita Philip, Mohammad Imran, Stephen L Yu, Hongxia Li, Philip C Amrein, Vu H Duong, Edward A Sausville, Maria R Baer, Amir T Fathi, Zeba Singh, Søren M Bentzen
Depletion of glutamine (Gln) has emerged as a potential therapeutic approach in the treatment of acute myeloid leukemia (AML), as neoplastic cells require Gln for synthesis of cellular components essential for survival. Asparaginases deplete Gln, and asparaginase derived from Erwinia chrysanthemi (Erwinaze) appears to have the greatest glutaminase activity of the available asparaginases. In this Phase I study, we sought to determine the dose of Erwinaze that safely and effectively depletes plasma Gln levels to ≤ 120 μmol/L in patients with relapsed or refractory (R/R) AML...
November 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29113211/aberrant-expression-of-cd133-and-cd82-in-patients-with-pediatric-acute-lymphoblastic-leukemia-and-the-clinical-significance
#7
Hongyan Ji, Li Chen, Yunpeng Dai, Xiaojun Sun, Xiuli Li, Qi Wang, Daoxin Ma, Dongdong Du, Ping Zhao, Yulin Wang
Cluster of differentiation (CD)133 is considered to be a marker of leukemia stem cells (LSCs), which are one of the primary causes of occurrence, drug resistance and relapse of acute lymphoblastic leukemia (ALL). CD82, an adhesion molecule, performs an important role in the interaction between LSCs and their niche. The purpose of the present study was to assess CD133 and CD82 expression in patients with pediatric ALL, and to evaluate the association with the clinical data. Using flow cytometric assessment and reverse transcription-polymerase chain reaction, CD133 and CD82 expression levels were measured in the bone marrow (BM) of 37 patients with newly diagnosed (ND) pediatric ALL [ALL-ND; 30 B-cell-ALL (B-ALL) and 7 T-cell-ALL (T-ALL)], in 22 patients with complete remission pediatric ALL (ALL-CR) and in 16 age-matched children without BM disease...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112013/cancer-therapy-associated-lymphoproliferative-disorders-an-under-recognized-type-of-immunodeficiency-associated-lymphoproliferative-disorder
#8
Sergio Pina-Oviedo, Roberto N Miranda, L Jeffrey Medeiros
We describe the clinicopathologic features of 17 patients who had a hematologic malignancy of various types, were treated, and subsequently developed a lymphoproliferative disorder (LPD). There were 10 men and 7 women with a median age of 59 years (range, 36 to 83 y). The primary hematologic neoplasms included: 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, 3 plasma cell myeloma, 2 acute monoblastic leukemia, and 1 case each of mixed-phenotype acute leukemia, chronic myeloid leukemia, splenic marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, T-cell prolymphocytic leukemia, and peripheral T-cell lymphoma...
November 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29108368/phase-i-clinical-trial-of-the-base-excision-repair-inhibitor-methoxyamine-in-combination-with-fludarabine-for-patients-with-advanced-hematologic-malignancies
#9
Paolo F Caimi, Brenda W Cooper, Basem M William, Afshin Dowlati, Paul M Barr, Pingfu Fu, John Pink, Yan Xu, Hillard M Lazarus, Marcos de Lima, Stanton L Gerson
Purpose: We determined the safety, pharmacokinetics, pharmacodynamics and recommended phase II dose of the base excision repair blocker methoxyamine combined with fludarabine. Materials and Methods: This was a phase I study with intravenous fludarabine (25 mg/m(2), days 1-5), and methoxyamine (15 mg/m(2)-120 mg/m(2), once). A maximum of six cycles were given. Adult patients with relapsed/refractory hematologic malignancies, excluding acute myeloid leukemia, were eligible...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108331/the-role-of-frontline-autologous-stem-cell-transplantation-for-primary-plasma-cell-leukemia-a-retrospective-multicenter-study-kmm160
#10
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...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099493/pharmacodynamics-and-proteomic-analysis-of-acalabrutinib-therapy-similarity-of-on-target-effects-to-ibrutinib-and-rationale-for-combination-therapy
#11
V K Patel, B Lamothe, M L Ayres, J Gay, J Cheung, K Balakrishnan, C Ivan, J Morse, M Nelson, M J Keating, W G Wierda, J R Marszalek, V Gandhi
Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL), however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation, and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens...
November 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29089618/circulating-exosomes-carrying-an-immunosuppressive-cargo-interfere-with-cellular-immunotherapy-in-acute-myeloid-leukemia
#12
Chang-Sook Hong, Priyanka Sharma, Saigopalakrishna S Yerneni, Patricia Simms, Edwin K Jackson, Theresa L Whiteside, Michael Boyiadzis
Exosomes, small (30-150 nm) extracellular vesicles (EVs) isolated from plasma of patients with acute myeloid leukemia (AML) carry leukemia-associated antigens and multiple inhibitory molecules. Circulating exosomes can deliver suppressive cargos to immune recipient cells, inhibiting anti-tumor activities. Pre-therapy plasma of refractory/relapsed AML patients contains elevated levels of immunosuppressive exosomes which interfere with anti-leukemia functions of activated immune cells. We show that exosomes isolated from pre-therapy plasma of the AML patients receiving adoptive NK-92 cell therapy block anti-leukemia cytotoxicity of NK-92 cells and other NK-92 cell functions...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080983/autoimmune-responses-to-exosomes-and-candidate-antigens-contribute-to-type-1-diabetes-in-non-obese-diabetic-mice
#13
REVIEW
Yang D Dai, Huiming Sheng, Peter Dias, M Jubayer Rahman, Roman Bashratyan, Danielle Regn, Kristi Marquardt
PURPOSE OF REVIEW: The initial autoimmune trigger of type 1 diabetes (T1D) remains unclear. In non-obese diabetic (NOD) mice, islet inflammation starts early in life, suggesting the presence of an endogenous trigger for the spontaneous autoimmune response in this T1D mouse model. In this review, we argue that abnormal release of exosomes might be the trigger of the early inflammatory and autoimmune responses in the islets. RECENT FINDINGS: Exosomes are nano-sized membrane complexes that are secreted by cells following fusion of late endosomes and/or multivesicular bodies with the plasma membrane...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29066491/igm-myeloma-with-plasma-cell-leukemia-case-report-and-literature-review
#14
Saurabh Chhabra, Sandeep Jain, Amanda Fowler, Valeriy Sedov, Amarendra K Neppalli, Cynthia A Schandl, John Lazarchick
IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation. Plasma cell leukemia (PCL) is a rare and aggressive variant of MM characterized by the presence of circulating plasma cells. We present a case report of a patient who presented with IgM MM in primary PCL phase with high-risk cytogenetics...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29064593/combination-therapy-incorporating-bcl-2-inhibition-with-venetoclax-for-the-treatment-of-refractory-primary-plasma-cell-leukemia-with-t-11-14
#15
Wilson I Gonsalves, Francis K Buadi, Shaji K Kumar
Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, i.e. t (11;14). Results from early phase clinical trials utilizing the selective bcl-2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating bcl-2 inhibition with daratumumab, bortezomib, venetoclax and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease...
October 24, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29064484/jam-a-as-a-prognostic-factor-and-new-therapeutic-target-in-multiple-myeloma
#16
A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis...
September 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29061822/in-vitro-effects-of-bromoalkyl-phenytoin-derivatives-on-regulated-death-cell-cycle-and-ultrastructure-of-leukemia-cells
#17
Katarzyna Śladowska, Małgorzata Opydo-Chanek, Teodora Król, Wojciech Trybus, Ewa Trybus, Anna Kopacz-Bednarska, Jadwiga Handzlik, Katarzyna Kieć-Kononowicz, Lidia Mazur
BACKGROUND/AIM: To search for new antileukemic agents, the chemical structure of phenytoin was modified. A possible cytotoxic activity of three bromoalkyl phenytoin analogs, methyl 2-(1-(3-bromopropyl)-2,4-dioxo-5,5-diphenylimidazolidin-3-yl) propanoate (PH2), 1-(3-bromopropyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (PH3) and 1-(4-bromobutyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione (PH4) on regulated cell death, the cell cycle and cell ultrastructure was assessed. MATERIALS AND METHODS: The experiments were performed in vitro on HL-60 and U937 cells, using flow cytometry and electron microscopy methods...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29061820/comparison-of-in-vitro-antileukemic-activity-of-4-hydroperoxyifosfamide-and-4-hydroperoxycyclophosphamide
#18
COMPARATIVE STUDY
Malgorzata Opydo-Chanek, Katarzyna Śladowska, Kamil Blicharski, Jaromir Mikeš, Peter Fedoročko, Ulf Niemeyer, Lidia Mazur
BACKGROUND/AIM: The oxazaphosphorines, ifosfamide and cyclophosphamide, represent a class of alkylating agents. The aim of the present in vitro study was to compare antileukemic activity of 4-hydroperoxyifosfamide (4-OOH-IF) and 4-hydroperoxycyclophosphamide (4-OOH-CP). MATERIALS AND METHODS: The experiments were performed on MOLT-4 and ML-1 cells. The research was conducted using flow cytometry fluorescein diacetate/propidium iodide (PI), fluorescein-conjugated annexin V/PI, CaspGLOW Red Active Caspase-8 and -9, CellEvent™ Caspase-3/7 Green assays, and tetramethylrhodamine ethyl ester test...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29059151/neurotensin-receptor-type-2-protects-b-cell-chronic-lymphocytic-leukemia-cells-from-apoptosis
#19
A Abbaci, H Talbot, S Saada, N Gachard, J Abraham, A Jaccard, D Bordessoule, A L Fauchais, T Naves, M O Jauberteau
B-cell chronic lymphocytic leukemia (B-CLL) cells are resistant to apoptosis, and consequently accumulate to the detriment of normal B cells and patient immunity. Because current therapies fail to eradicate these apoptosis-resistant cells, it is essential to identify alternative survival pathways as novel targets for anticancer therapies. Overexpression of cell-surface G protein-coupled receptors drives cell transformation, and thus plays a critical role in malignancies. In this study, we identified neurotensin receptor 2 (NTSR2) as an essential driver of apoptosis resistance in B-CLL...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29046749/an-unusual-case-of-chronic-lymphocytic-leukemia-multiple-myeloma-and-cardiac-amyloidosis
#20
Dongyan Liu, Hakim T Uqdah, Alisha D Gordy
Light chain amyloidosis has very rarely been reported in association with chronic lymphocytic leukemia (CLL). We reported on a 76-years-old female who presented with simultaneous kappa-restricted chronic lymphocytic leukemia (CLL) and a lambda-restricted multiple myeloma with plasma cells causing AL amyloidosis involving the heart. While monoclonal immunoglobulins occasionallyproduced by CLL have previously been implicated in AL amyloidosis, there only a few cases reported of AL amyloidosis resulting from a distinct plasma cell dyscrasia that is not clonally related to the concurrent CLL...
October 2017: Journal of Community Hospital Internal Medicine Perspectives
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