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Plasma cell leukemia

Lucia Pavlikova, Mario Seres, Denisa Imrichova, Milan Hano, Andrej Rusnak, Martina Zamorova, Jaroslav Katrlik, Albert Breier, Zdena Sulova
In P-gp-positive cell variants obtained from L1210 cells either by selection with vincristine (L1210/R) or by transfection with the human gene encoding P-gp (L1210/T), we have previously described cross-resistance to tunicamycin (TNM), a protein N-glycosylation inhibitor. Here we studied whether this cross-resistance also underlies P-gp-positive variants of human acute myeloid leukemia cells (AML) derived from SKM-1 and MOLM-13 cells (SKM-1/VCR, SKM-1/LEN, MOLM-13/VCR) by selection with vincristine (VCR) and lenalidomide (LEN)...
October 2016: General Physiology and Biophysics
Antonino Neri, Katia Todoerti, Marta Lionetti, Vittorio Simeon, Marzia Barbieri, Filomena Nozza, Gabriella Vona, Alessandra Pompa, Luca Baldini, Pellegrino Musto
Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. The introduction of novel agents and modern technologies has recently partially changed the clinical and biological scenario of this malignancy, allowing limited, but not negligible, progresses. Areas covered: We will discuss the complex landscape of genetic alterations in PPCL, derived from conventional and high-throughput technologies; the best available treatments for PPCL; the possible future therapeutic perspectives...
October 19, 2016: Expert Review of Hematology
P Pardes-Chavanes, M Afanetti, C Boyer, M Poirée
Intracerebral hemorrhage (ICH) remains a cause of death in hematologic malignancies. Asparaginase represents a key agent in the treatment of acute lymphoblastic leukemia (ALL). The toxicity of asparaginase includes coagulopathy such as thrombotic or bleeding tendency. We report a case of fatal cerebral hemorrhage in a 12-year-old girl treated for ALL. Cerebral hemorrhage occurred after three injections of L-asparaginase. The patient presented with hypofibrinogenemia (0.36g/L), associated with thrombocytopenia (24,000/mm(3))...
October 12, 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Imran N Ahmad, Salman Assad, Muhammad Rahman, Haider Ghazanfar
PURPOSE:   This study summarizes a four-year experience from the analysis of hematolymphoid malignancies in Pakistani population using a database of six-colored flow cytometry. METHODS: A cross-sectional survey of 323 specimens of hematolymphoid malignancies using six-colored flow cytometry (FC) was carried out in Shifa International Hospital, Islamabad, Pakistan from June 2012 to June 2016. The criterion for specimen adequacy was that the cases have abnormal populations by FC, and the specimen age (time from biopsy to being examined by the six-color FC tube) of three days or less was to be included in the study...
September 1, 2016: Curēus
Xianjin Zhu, Yanfang Song, Conglian Wu, Chuxi Pan, Pingxia Lu, Meihua Wang, Peizheng Zheng, Rongfen Huo, Chenqing Zhang, Wanting Li, Yulin Lin, Yingping Cao, Ningli Li
Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients...
October 11, 2016: Scientific Reports
Hao Zhang, Weipeng Su, Zhixiong Ying, Yueping Chen, Le Zhou, Yue Li, Jingfei Zhang, Lili Zhang, Tian Wang
PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1...
October 8, 2016: European Journal of Nutrition
Prithal Gangadhar, Zulfikar Ahmed, Muktha R Pai, I Sandhya
Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma accounting for 2-3% of all plasma cell dyscrasias characterized by the presence of circulating plasma cells. The diagnosis is based on the % (≥20%) and absolute number (≥2x10 9 /L) of plasma cells in the peripheral blood. The incidence of primary PCL (pPCL) is very rare and reported to occur in <1 in a million. It is classified as either pPCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. pPCL is a distinct clinicopathological entity with different cytogenetic and molecular findings...
October 2016: Indian Journal of Pathology & Microbiology
Yan Wang, Ling Zhou, Meng Xiao, Zhong-Liang Sun, Chang-Yuan Zhang
In the present study, we have synthesized an amphiphilic pH-sensitive structure of poly(ethylene glycol) methyl ether-b-(poly lactic acid-co-poly(b-amino esters)) (MPEG-b-(PLA-co-PAE)) to load paclitaxel to increase the therapeutic efficacy in leukemia. The micelles exhibit excellent drug-loading capacities for paclitaxel (PTX) and exhibited a typical pH-responsive drug release pattern. The release of PTX from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0 which just fitted the pathological process...
September 13, 2016: Colloids and Surfaces. B, Biointerfaces
Victor Peperzak, Erik Slinger, Johanna Ter Burg, Eric Eldering
For successful treatment of malignant B-cells it is crucial to understand intrinsic survival requirements in relation to their normal progenitors. Long-lived humoral immunity as well as most B-cell malignancies, originate in the germinal center (GC). Murine GC B-cells depend on pro-survival protein MCL-1, but not BCL-XL. In contrast, naive and memory B-cells depend on BCL-2, but not BCL-XL or MCL-1. For human B-cell subsets, the functional relationships among BCL-2 members are unclear, and also if and how they shift after malignant transformation...
September 30, 2016: Cell Death and Differentiation
Daria Sollazzo, Dorian Forte, Nicola Polverelli, Margherita Perricone, Marco Romano, Simona Luatti, Nicola Vianelli, Michele Cavo, Francesca Palandri, Lucia Catani
Myelofibrosis (MF) is a clonal neoplasia of the hemopoietic stem/progenitor cells associated with genetic mutations in the Janus kinase 2 (JAK2), myeloproliferative leukemia virus oncogene (MPL), and calreticulin (CALR) genes. MF is also characterized by a state of chronic inflammation. Calreticulin (CRT), as a multifunctional protein, is involved in a spectrum of cellular processes including inflammation, autoimmunity, and cancer initiation/progression. Based on this background, we hypothesised that in MF circulating CRT might reflect the inflammatory process...
2016: Mediators of Inflammation
C I E Smith
BTK is a cytoplasmic protein-tyrosine kinase, whose corresponding gene was isolated in the early 1990s. BTK was initially identified by positional cloning of the gene causing X-linked agammaglobulinemia and independently in a search for new kinases. Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity...
September 26, 2016: Oncogene
Andrew S Artz, Brent Logan, Xiaochun Zhu, Gorgun Akpek, Rodrigo Martino Bufarull, Vikas Gupta, Hillard M Lazarus, Mark Litzow, Alison Loren, Navneet S Majhail, Richard T Maziarz, Philip McCarthy, Uday Popat, Wael Saber, Stephen Spellman, Olle Ringden, Amittha Wickrema, Marcelo C Pasquini, Kenneth R Cooke
We sought to confirm the prognostic importance of simple clinically available biomarkers of c-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin...
August 4, 2016: Haematologica
Deeksha Vishwamitra, Suraj Konnath George, Ping Shi, Ahmed O Kaseb, Hesham M Amin
The insulin-like growth factor (IGF) signaling system plays key roles in the establishment and progression of different types of cancer. In agreement with this idea, substantial evidence has shown that the type I IGF receptor (IGF-IR) and its primary ligand IGF-I are important for maintaining the survival of malignant cells of hematopoietic origin. In this review, we discuss current understanding of the role of IGF-IR signaling in cancer with a focus on the hematological neoplasms. We also address the emergence of IGF-IR as a potential therapeutic target for the treatment of different types of cancer including plasma cell myeloma, leukemia, and lymphoma...
September 19, 2016: Oncotarget
Renate Burger, Andreas Guenther, Katja Klausz, Matthias Staudinger, Matthias Peipp, Eva Maria Murga Penas, Stefan Rose-John, John Wijdenes, Martin Gramatzki
Interleukin (IL)-6 has an important role in the pathophysiology of multiple myeloma where it supports the growth and survival of the malignant plasma cells in the bone marrow. It belongs to a family of cytokines which use the glycoprotein (gp)130 chain for signal transduction, such as oncostatin M or leukemia inhibitory factor (LIF). Targeting IL-6 in plasma cell diseases is currently evaluated in clinical trials with monoclonal antibodies (mAbs). Here, efforts were made to elucidate the contribution of IL-6 and gp130 signaling in malignant plasma cell growth in vivo...
September 22, 2016: Haematologica
Clément Chevalier, Serge Roche, Christine Bénistant
ERBB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) amplification is associated with invasive breast cancer. We discovered that TOM1L1 (target of myb1-like 1) and ERBB2 co-amplification defines a novel mechanism involved in breast cancer metastatic progression. Upregulation of the vesicular trafficking protein TOM1L1 enhances plasma membrane delivery of membrane-type 1 matrix metalloprotease (MT1-MMP) for efficient extracellular matrix degradation and tumor cell dissemination.
July 2016: Molecular & Cellular Oncology
Martin Ellis, Eilon Krashin, Orly Hamburger-Avnery, Sarah Gan, Avishai Elis, Osnat Ashur-Fabian
Imatinib, which has revolutionized chronic myeloid leukemia (CML) treatment, was suggested to improve lipid profile. Statins, a dyslipidemia drug, were reported to potentiate imatinib's antileukemic effect. However, analysis of imatinib combined with statins is lacking. We have retrospectively analyzed the normalization period of bcr-abl, blood counts, and lipids in 40 CML patients, 19 of which co-treated with statins, during short (<12 months) and prolonged (>12 months) imatinib treatment. Prior statins treatment did not hinder nor sensitized imatinib's anti-leukemic and lipid-lowering effects...
September 21, 2016: Leukemia & Lymphoma
Leire Iparraguirre, Angela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Itziar Astigarraga, Aurora Navajas, Ana Sastre, Nagore Garcia de Andoin, Africa Garcia-Orad
OBJECTIVES: Methotrexate (MTX), the key drug in childhood B-cell acute lymphoblastic leukemia (B-ALL) therapy, often causes toxicity. An association between genetic variants in MTX transport genes and toxicity has been found. It is known that these transporters are regulated by microRNAs (miRNAs), and miRNA single nucleotide polymorphisms (SNPs) interfere with miRNA levels or function. With regard to B-cell ALL, we have previously found rs56103835 in miR-323b that targets ABCC4 associated with MTX plasma levels...
November 2016: Pharmacogenetics and Genomics
Lauren R Teras, Carol E DeSantis, James R Cerhan, Lindsay M Morton, Ahmedin Jemal, Christopher R Flowers
Collectively, lymphoid neoplasms are the fourth most common cancer and the sixth leading cause of cancer death in the United States. The authors provide contemporary lymphoid neoplasm statistics by subtype based on the 2008 World Health Organization classifications, including the most current US incidence and survival data. Presented for the first time are estimates of the total numbers of US lymphoid neoplasm cases by subtype as well as a detailed evaluation of incidence and survival statistics. In 2016, 136,960 new lymphoid neoplasms are expected...
September 12, 2016: CA: a Cancer Journal for Clinicians
Hadeel A Khalil, Tarek S Belal, Ahmed F El-Yazbi, Dalia A Hamdy
BACKGROUND: Vincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor diseases. Recently, high incidence of hyperlipidemia was reported to be associated with allogenic hematopoietic stem cell transplantation and VCR/L-asparaginase therapy. The aim of this study is to test the effects of incremental increase in lipoproteins levels on vincristine disposition in rat. METHOD: To study VCR pharmacokinetics and protein binding, rats (n = 25) were assigned to three groups, normal lipidemic (NL), intermediate (IHL) and extreme hyperlipidemic (HL)...
2016: Lipids in Health and Disease
Noah I Hornick, Ben Doron, Sherif Abdelhamed, Jianya Huan, Christina A Harrington, Rongkun Shen, Xiaolu A Cambronne, Santhosh Chakkaramakkil Verghese, Peter Kurre
Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155...
2016: Science Signaling
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