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https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#1
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
July 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28693234/relapsed-anaplastic-lymphoma-kinase-positive-large-b-cell-lymphoma-expressed-cluster-of-differentiation-4-and-cytokeratin-an-initially-misdiagnosed-case-corrected-by-immunoglobulin-%C3%AE%C2%BA-locus-gene-rearrangement-detection
#2
Yunfei Shi, Xianghong Li, Yuqin Song, Lixin Zhou, Qin Feng, Ping Wang, Chen Zhang, Weiping Liu, Yanhua Bai, Yumei Lai
Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare lymphoma subtype. The present study investigated a refractory nodal ALK-positive LBCL case in a 28-year-old Chinese male. It was initially misdiagnosed as ALK-positive anaplastic large cell lymphoma; however, the patient's lesions relapsed and spread widely following a short remission for chemotherapy and the patient succumbed to the disease 3 months' post-autologous stem cell transplantation; thus, a revision was performed. Histologically, the tumor cells exhibited a characteristic immunoblastic morphology with marked cellular pleomorphism...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28679988/follicular-lymphoma-with-plasmacytic-differentiation-accompanied-by-monoclonal-igg-gammopathy
#3
Tomomi Oka, Masayuki Kobayashi, Takaya Komori, Hirokazu Nakamine, Toshiyuki Kitano, Masakatsu Hishizawa, Tadakazu Kondoh, Kouhei Yamashita, Akifumi Takaori-Kondo
A 59-year-old woman presented with high serum total protein, detected on a screening examination. Laboratory tests revealed high plasma levels of M-protein (IgG-λ), and FDG-PET/CT revealed systemic lymph node swelling and a large tumorous mass in the abdominal cavity. Bone marrow aspirates contained 8.4% plasma cells and approximately 30% abnormal small lymphocytes. A biopsy of the left supraclavicular lymph node was initially interpreted as lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the lymph node demonstrated an unusual karyotype with t (14;18) (q32;q21)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28678330/a-correlation-study-between-igh-gene-rearrangement-and-orbital-lymphoma-removal-operation-prognosis
#4
B Ding, Z-C Ju, J-M Liu
OBJECTIVE: To explore the relationship between IgH gene rearrangement and orbital MALT (mucose-associated lymphoid tissue) lymphoma removal operation prognosis, and to quantify the effect of IgH gene rearrangement on primary orbital MALT lymphoma prognosis. PATIENTS AND METHODS: Fifty-eight patient cases with primary orbital MALT lymphoma were included in this study. Orbital lymphoma specimens were embedded in paraffin for sectioning. IgH gene rearrangement was detected using PCR...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28664940/clinical-implications-of-cytogenetic-heterogeneity-in-multiple-myeloma-patients-with-tp53-deletion
#5
Suyang Hao, Pei Lin, L Jeffrey Medeiros, Lianghua Fang, Adrian A Carballo-Zarate, Sergej N Konoplev, Rachel L Sargent, Donna M Weber, Sheeba K Thomas, Elisabet E Manasanch, Robert Z Orlowski, Xinyan Lu
TP53 deletion (ΔTP53) in myeloma is known to be a high-risk finding associated with poorer prognosis. The prognostic impact of underlying cytogenetic heterogeneity in patients with myeloma associated with ΔTP53 is unknown. We studied 90 patients with myeloma associated with ΔTP53 identified by interphase fluorescence in situ hybridization and assessed the impact of karyotype and coexisting alterations of IGH, RB1, and CKS1B. There were 54 men and 36 women with a median age of 59 years (range 38-84); 14 patients had a normal karyotype (NK/ΔTP53), 73 had a complex karyotype (CK/ΔTP53), and 3 had a non-complex abnormal karyotype...
June 30, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28652011/development-and-evaluation-of-polyclonal-antisera-for-detection-of-the-igm-heavy-chain-of-multiple-fish-species
#6
Walissara Jirapongpairoj, Ikuo Hirono, Hidehiro Kondo
Antibodies are widely considered to be essential tools for detection of immune responses in various fish species. Here we produced the peptide polyclonal antisera (anti-fish IgH-1 and anti-fish IgH-2) to detect IgM of various fish species. The peptides were designed based on the conserved sequence of the fish immunoglobulin heavy chains of seven fish species (Japanese flounder, seabream, yellowtail, carp, rainbow trout, hybrid sturgeon and banded houndshark). By Western blotting, anti-fish IgH-1 antiserum detected the IgMs of all fish species except banded houndshark...
June 23, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28645875/high-resolution-igh-repertoire-analysis-reveals-fetal-liver-as-the-likely-origin-of-life-long-innate-b-lymphopoiesis-in-humans
#7
Anindita Roy, Vojtech Bystry, Georg Bohn, Katerina Goudevenou, Tomas Reigl, Maria Papaioannou, Adam Krejci, Sorcha O'Byrne, Aristeidis Chaidos, Andrea Grioni, Nikos Darzentas, Irene A G Roberts, Anastasios Karadimitris
The ontogeny of the natural, public IgM repertoire remains incompletely explored. Here, high-resolution immunogenetic analysis of B cells from (unrelated) fetal, child, and adult samples, shows that although fetal liver (FL) and bone marrow (FBM) IgM repertoires are equally diversified, FL is the main source of IgM natural immunity during the 2nd trimester. Strikingly, 0.25% of all prenatal clonotypes, comprising 18.7% of the expressed repertoire, are shared with the postnatal samples, consistent with persisting fetal IgM+ B cells being a source of natural IgM repertoire in adult life...
June 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28641644/-clinical-significance-of-mean-platelet-volume-determination-in-multiple-myeloma
#8
Peng Gao, Zhong-Ping Xiao, Kun Fu, Mei Han
OBJECTIVE: To investigate the clinical significance of mean platelet volume(MPV) in patients with multiple myeloma(MM). METHODS: The clinical data of 198 patients with MM admitted in our hospital from March 2008 to March 2015 were collected and analyzed. The clinical data included the Ig type, hemoglobin level, platelet count, creatinine, calciumion albumin, β2-MG, LDH, plasmocytes in bone marrow, MPV, complications such as diabetes, a history of venous thromboembolism (VTE) and arterial events such as coronary artery disease, cerebrovascular disease, thrombosis and blood clotting...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641640/-application-of-cd138-immunomagnetic-sorting-myeloma-cells-combined-with-fluorescence-in-situ-hybridization-for-detecting-cytogenetic-abnormalities-of-multiple-myeloma
#9
Lu Gao, Qing Liu, Yan Shi, Hui Dang, Qi He, Zheng Wang, Lin Feng, Ye Li, Xiao-Yan Wang, Na Li, Wen-Jie Song, Yan-Lin Wang, Shu Kong, Jin Lu, Xiao-Jun Huang, Yue-Yun Lai
OBJECTIVE: To investigate the efficiency of direct fluorescence in situ hybridization (D-FISH) versus FISH on CD138 immunomagnetic sorting myeloma cells (MACS-FISH) to detect the cytogenetic abnormalities of multiple myeloma. METHODS: Thirty-one patients with multiple myeloma (MM) were detected by D-FISH and MACS-FISH, using 5 probes, including 1q21, D13S319, RB1, IgH, P53. The IgH rearrangement positive patients were further examined by 3 IgH rearrangement subtype FISH probes including IgH/FGFR3, IgH/MAF and IgH/CCND1...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641141/rag2-involves-the-ig%C3%AE%C2%BA-locus-demethylation-during-b-cell-development
#10
Caijun Wu, Yanying Dong, Xiaohui Zhao, Ping Zhang, Mingzhe Zheng, Hua Zhang, Shichang Li, Yaofeng Jin, Yunfeng Ma, Huixun Ren, Yanhong Ji
The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28640838/next-generation-sequencing-of-the-clonal-igh-rearrangement-detects-ongoing-mutations-and-interfollicular-trafficking-in-in-situ-follicular-neoplasia
#11
Perikles Kosmidis, Irina Bonzheim, Claudia Dufke, Sema Colak, Thomas Hentrich, Christopher Schroeder, Peter Bauer, Patrick Adam, Falko Fend
Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL...
2017: PloS One
https://www.readbyqxmd.com/read/28634224/igh-myc-translocation-associates-with-brca2-deficiency-and-synthetic-lethality-to-parp1-inhibitors
#12
Silvia Maifrede, Kayla Martin, Paulina Podszywalow-Bartnicka, Katherine Sullivan, Samantha K Langer, Reza Nejadi, Yashodhara Dasgupta, Michael Hulse, Daniel Gritsyuk, Margaret Nieborowska-Skorska, Lena N Lupey-Green, Huaqing Zhao, Katarzyna Piwocka, Mariusz A Wasik, Italo Tempera, Tomasz Skorski
Burkitt lymphoma/leukemia (BL) cells carry t(8;14)(q24;q32) chromosomal translocation encoding IGH/MYC, which results in the constitutive expression of the MYC oncogene. Here, it is demonstrated that untreated and cytarabine (AraC)-treated IGH/MYC-positive BL cells accumulate a high number of potentially lethal DNA double-strand breaks (DSBs) and display low levels of the BRCA2 tumor suppressor protein, which is a key element of homologous recombination (HR)-mediated DSB repair. BRCA2 deficiency in IGH/MYC-positive cells was associated with diminished HR activity and hypersensitivity to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors (olaparib, talazoparib) used alone or in combination with cytarabine in vitro...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28628107/identification-of-sequence-variants-influencing-immunoglobulin-levels
#13
Stefan Jonsson, Gardar Sveinbjornsson, Aitzkoa Lopez de Lapuente Portilla, Bhairavi Swaminathan, Rosina Plomp, Gillian Dekkers, Ram Ajore, Mina Ali, Arthur E H Bentlage, Evelina Elmér, Gudmundur I Eyjolfsson, Sigurjon A Gudjonsson, Urban Gullberg, Arnaldur Gylfason, Bjarni V Halldorsson, Markus Hansson, Hilma Holm, Åsa Johansson, Ellinor Johnsson, Aslaug Jonasdottir, Bjorn R Ludviksson, Asmundur Oddsson, Isleifur Olafsson, Sigurgeir Olafsson, Olof Sigurdardottir, Asgeir Sigurdsson, Lilja Stefansdottir, Gisli Masson, Patrick Sulem, Manfred Wuhrer, Anna-Karin Wihlborg, Gudmar Thorleifsson, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Gestur Vidarsson, Ingileif Jonsdottir, Björn Nilsson, Kari Stefansson
Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8...
June 19, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28624792/mb4-2-mb4-3-transcripts-of-igh-mmset-fusion-gene-in-t-4-14-pos-multiple-myeloma-indicate-poor-prognosis
#14
Feng Li, Yong-Ping Zhai, Ting Lai, Qian Zhao, Hui Zhang, Yu-Mei Tang, Jian Hou
Multiple myeloma (MM) patients with t(4;14) is a heterogeneous group. Prognostic tools capable of predicting the outcome of patients are currently lacking. The MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. This study analyzed whether the overexpression of full-length (MB4-1) or truncated forms (MB4-2 and MB4-3) of MMSET influence the prognosis of t(4;14)pos MM patients. A total of 53 symptomatic t(4;14)pos MM patients were retrospectively analyzed...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624474/-exposure-to-the-insecticides-permethrin-and-malathion-induces-leukemia-and-lymphoma-associated-gene-aberrations-in-vitro
#15
M P Navarrete-Meneses, C Salas-Labadía, M Sanabrais-Jiménez, J Santana-Hernández, A Serrano-Cuevas, R Juárez-Velázquez, A Olaya-Vargas, P Pérez-Vera
Epidemiological studies have associated the exposure to permethrin and malathion with increased risk of leukemia and lymphoma. The aim of this study was to evaluate whether in vitro exposure to permethrin and malathion induces aberrations in genes involved in the etiology of these hematological malignancies. Genetic abnormalities in the IGH, KMT2A (MLL), ETV6 and RUNX1 genes, and aneuploidy induced by the in vitro exposure to permethrin and malathion (200μM, 24h), were analyzed by FISH in peripheral blood mononuclear cells (PBMCs)...
June 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28614781/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#16
Simar Pal Singh, Saravanan Y Pillai, Marjolein J W de Bruijn, Ralph Stadhouders, Odilia B J Corneth, Henk Jan van den Ham, Alice Muggen, Wilfred van IJcken, Erik Slinger, Annemieke Kuil, Marcel Spaargaren, Arnon P Kater, Anton W Langerak, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be adoptively transferred into Rag1-/- mice...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595732/the-novel-double-hit-t-8-22-q24-q11-myc-igl-and-t-14-15-q32-q24-igh-bcl2a1-in-diffuse-large-b-cell-lymphoma
#17
Takashi Akasaka, Chiyuki Kishimori, Katsuhiro Fukutsuka, Miho Nakagawa, Kayo Takeoka, Masahiko Hayashida, Gen Honjo, Hitoshi Ohno
An 82-year-old woman presented with generalized lymphadenopathy and skin involvement. Lymph node biopsy revealed diffuse large B-cell lymphoma with a high proliferation index. G-banding and fluorescence in situ hybridization showed a hypertetraploid karyotype with two copies of t(8;22)(q24;q11), generating the fusion of MYC and the immunoglobulin λ chain gene (IGL), and two copies of the novel immunoglobulin heavy chain gene (IGH) translocation, t(14;15)(q32;q24). A long-distance inverse polymerase chain reaction (PCR) using nested primer combinations designed for each constant gene of IGH showed that Cγ4 was juxtaposed to the downstream sequence of the BCL2A1 (BCL2-related protein A1) gene through the Sγ4 switch region...
August 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28592757/hiv-negative-plasmablastic-lymphoma-attaining-sustained-remission-with-bortezomib-combined-dose-adjusted-epoch-therapy
#18
Hiroyuki Kobayashi, Norito Miyagi
A 61-year-old, HIV-negative, immunocompetent woman was admitted to our hospital for significant weight loss, painful swelling of her right cheek, and rapid growth of a tumor in the right hard palate. A CT scan revealed a neoplastic lesion in the right maxillary sinus, extending to the surrounding soft bone tissue and oral cavity, as well as multiple osteolytic lesions in the skull. A pathologic examination revealed that the neoplastic cells in the oral cavity were plasmablasts tending to appear as differentiated plasma cells...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28582596/a-metastatic-secretory-gastric-plasmacytoma-with-aberrant-cd3-expression-in-a-dog
#19
Matthew J Atherton, Samantha Vazquez-Sanmartin, Sam Sharpe, Elspeth M Waugh, Joanna S Morris
A 10-year-old crossbred dog was presented with a 6-week history of hematemesis, melena, anorexia, and lethargy. Clinical evaluation revealed a gastric mass with a regional lymphadenomegaly as well as a monoclonal gammopathy manifesting as hyperglobulinemia. Cytologic and histopathologic analyses were consistent with a round cell neoplasm; neoplastic cells showed nuclear immunoreactivity for MUM1 and diffuse cytoplasmic reactivity for CD3. Polymerase chain reactions performed on fixed and fresh tissue identified a clonal rearrangement with an IgH primer set...
June 5, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28557599/validation-of-oncopanel-a-targeted-next-generation-sequencing-assay-for-the-detection-of-somatic-variants-in-cancer
#20
Elizabeth P Garcia, Alissa Minkovsky, Yonghui Jia, Matthew D Ducar, Priyanka Shivdasani, Xin Gong, Azra H Ligon, Lynette M Sholl, Frank C Kuo, Laura E MacConaill, Neal I Lindeman, Fei Dong
CONTEXT: - The analysis of somatic mutations across multiple genes in cancer specimens may be used to aid clinical decision making. The analytical validation of targeted next-generation sequencing panels is important to assess accuracy and limitations. OBJECTIVE: - To report the development and validation of OncoPanel, a custom targeted next-generation sequencing assay for cancer. DESIGN: - OncoPanel was designed for the detection of single-nucleotide variants, insertions and deletions, copy number alterations, and structural variants across 282 genes with evidence as drivers of cancer biology...
June 2017: Archives of Pathology & Laboratory Medicine
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