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https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-human-leukocyte-antigen-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplant-for-chronic-lymphocytic-leukemia-cll
#1
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplant (allo-HCT) for medically fit patients. Although the use of allo-HCT has reduced since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT as it represents the only known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28984869/bcl2-and-mir-15-16-from-gene-discovery-to-treatment
#2
REVIEW
Yuri Pekarsky, Veronica Balatti, Carlo M Croce
In 1984, we investigated the t(14;18) chromosomal translocations that frequently occur in patients with follicular lymphoma. We first identified a locus on chromosome 18 involved in these translocations with the chromosome 14 containing the immunoglobulin heavy chain locus. Within this region on chromosome 18, we then discovered a gene that we called BCL2, which was activated by the translocations. Since that time, many studies determined that BCL2 is one of the most important oncogenes involved in cancer by inhibiting apoptosis...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28983465/myc-immunohistochemistry-predicts-myc-rearrangements-by-fish
#3
Julum Nwanze, Momin T Siddiqui, Keith A Stevens, Debra Saxe, Cynthia Cohen
MYC is the proto-oncogene classically associated with Burkitt lymphoma (BL) located at chromosomal locus 8q24. Rearrangements of MYC are seen in nearly 100% of BL but have been reported in 3-16% of diffuse large B-cell lymphomas (DLBCLs). Rearrangements of MYC are tested for by flourescence in situ hybridization (FISH). In this study, we compared immunohistochemistry (IHC) using a monoclonal antibody directed against the human Myc protein to the current method, FISH. 31 cases were identified that had been tested for MYC rearrangements by FISH over 27 months with heterogeneity in the diagnoses: 5 BL; 10 DLBCL; 3 B-cell lymphoma unclassifiable between DLBCL and BL; 5 B-cell lymphoma not otherwise specified; 1 EBV-related B-cell lymphoma; 1 composite CLL/SLL-large cell lymphoma; and 6 designated as high-grade or aggressive B-cell lymphoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28978838/chronic-lymphocytic-leukemia-biology-disease-progression-and-current-treatment-strategies
#4
Takahiro Yano
Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and accumulation of mature CD5-positive, CD10-negative, CD20 weakly positive, and CD23-positive B-cells within blood, bone marrow, lymph nodes, and spleen. In proliferation centers, the survival and growth of CLL cells requires a permissive microenvironment comprising T-cells, macrophages, and stromal cells. FISH analysis has revealed that almost 80% of CLL cases carry chromosomal abnormalities including the most frequent del (13q14) and the strongest poor prognostic factor del (17p), both related to TP53 mutations...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28972595/ibrutinib-modulates-the-immunosuppressive-cll-microenvironment-through-stat3-mediated-suppression-of-regulatory-b-cell-function-and-inhibition-of-the-pd-1-pd-l1-pathway
#5
K Kondo, H Shaim, P A Thompson, J A Burger, M Keating, Z Estrov, D Harris, E Kim, A Ferrajoli, M Daher, R Basar, M Muftuoglu, N Imahashi, A Alsuliman, C Sobieski, E Gokdemir, W Wierda, N Jain, E Liu, E J Shpall, K Rezvani
Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naïve CLL. Besides directly inhibiting BTK, ibrutinib possesses immunomodulatory properties through targeting multiple signaling pathways. Understanding how this ancillary property of ibrutinib modifies the CLL microenvironment is crucial for further exploration of immune responses in this disease and devising future combination therapies. Here, we investigated the mechanisms underlying the immunomodulatory properties of ibrutinib...
October 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28972490/phagocytosis-and-expression-of-fcg-receptors-and-cd180-on-monocytes-in-chronic-lymphocytic-leukemia
#6
T Tsertsvadze, N Mitskevich, A Bilanishvili, D Girdaladze, N Porakishvili
Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disease characterised by accumulation of monoclonal CD19+CD5+CD23+ lymphocytes in the peripheral blood and bone marrow. CLL is the most common type of the adult leukemia in the Western world. The disease is incurable, albeit there are new molecular and immunotherapy methods currently available in conjunction with chemotherapy, leading to the "precision therapy". The majority of immunotherapeutic approaches are based on the ability of therapeutic antibodies (Rituximab, Alemtuzumab) to mobilize anti-tumour potential of the Natural Killer cells and macrophages/monocytes through their Fcg-receptors (FcγR)...
September 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28971904/cd40-signaling-instructs-chronic-lymphocytic-leukemia-cells-to-attract-monocytes-via-the-ccr2-axis
#7
Martijn H A van Attekum, Jaco A C van Bruggen, Erik Slinger, M Cristina Lebre, Emilie Reinen, Sabina Kersting, Eric Eldering, Arnon P Kater
Chronic lymphocytic leukemia cells are provided with essential survival and proliferative signals in the lymph node microenvironment. Here, chronic lymphocytic leukemia cells engage in various interactions with bystander cells such as T cells and macrophages. Phenotypically distinct types of tumor infiltrating macrophages can either be tumor supportive (M2) or play a role in tumor immune surveillance (M1). Although recent in vitro findings suggest a protective role for macrophages in chronic lymphocytic leukemia, the actual balance between these macrophage subsets in chronic lymphocytic leukemia lymphoid tissue is still unclear...
September 29, 2017: Haematologica
https://www.readbyqxmd.com/read/28945111/pi3k%C3%AE-selective-and-pi3k%C3%AE-%C3%AE-combinatorial-inhibitors-in-clinical-development-for-b-cell-non-hodgkin-lymphoma
#8
Benjamin L Lampson, Jennifer R Brown
The efficacy of the prototypical phosphatidylinositol-3-kinase (PI3K) inhibitor idelalisib for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) has led to development of multiple compounds targeting this pathway. Areas Covered: We review the hypothesized therapeutic mechanisms of PI3K inhibitors, including abrogation of B cell receptor signaling, blockade of microenvironmental pro-survival signals, and enhancement of anti-tumor immunity. We examine toxicities of idelalisib, including bacterial infections (possibly secondary to drug-induced neutropenia), opportunistic infections (possibly attributable to on-target inhibition of T cell function), and organ toxicities such as transaminitis and enterocolitis (possibly autoimmune, secondary to on-target inhibition of p110δ in regulatory T cells)...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28937430/cutaneous-richter-syndrome-mimicking-primary-cutaneous-cd4-positive-small-medium-t-cell-lymphoma-case-report-and-review-of-the-literature
#9
Miguel Rito, José Cabeçadas, Joaninha Costa Rosa, Mariana Cravo, Alistair Robson
Richter syndrome represents the transformation of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma into an aggressive large B-cell lymphoma. Skin involvement is exceptionally rare, with <20 cases reported and its presence as the first presentation of CLL/small lymphocytic lymphoma, as an isolated skin lesion has never been described. Primary cutaneous CD4-positive small/medium T-cell lymphoma (CD4 PCSM-TCL) characteristically presents with a dense dermal infiltrate consisting primarily of small-/medium-sized pleomorphic T-cells and less than 30% large pleomorphic cells...
September 12, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28935990/notch1-mutations-are-associated-with-high-cd49d-expression-in-chronic-lymphocytic-leukemia-link-between-the-notch1-and-the-nf-kb-pathways
#10
D Benedetti, E Tissino, F Pozzo, T Bittolo, C Caldana, C Perini, D Martorelli, V Bravin, T D'Agaro, F M Rossi, R Bomben, E Santinelli, F Zaja, G Pozzato, A Chiarenza, F Di Raimondo, G Del Poeta, D Rossi, G Gaidano, M Dal Bo, V Gattei, A Zucchetto
In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the VLA-4 integrin, a well-known key regulator of microenviromental interactions and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0...
September 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28935694/cellular-kinetics-of-ctl019-in-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia
#11
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28924241/clinical-impact-of-the-subclonal-architecture-and-mutational-complexity-in-chronic-lymphocytic-leukemia
#12
F Nadeu, G Clot, J Delgado, D Martín-García, T Baumann, I Salaverria, S Beà, M Pinyol, P Jares, A Navarro, H Suárez-Cisneros, M Aymerich, M Rozman, N Villamor, D Colomer, M González, M Alcoceba, M J Terol, B Navarro, E Colado, Á R Payer, X S Puente, C López-Otín, A López-Guillermo, A Enjuanes, E Campo
Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6-25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases...
September 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28833722/killing-two-birds-with-one-stone-response-to-pembrolizumab-in-a-patient-with-metastatic-melanoma-and-b-cell-chronic-lymphocytic-leukemia
#13
M Arenbergerova, A Fialova, P Arenberger, S Gkalpakiotis, T Jirasek, A Srp, A Novotna, H Frankova
Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody against PD-1, has demonstrated antitumor activity and a manageable safety profile in patients with different solid tumors and hematologic malignancies in multiple clinical trials (1-4). Although these data highlight the effectiveness of PD-1 pathway inhibition, some patients, even those with highly immunogenic tumors, such as melanoma, do not achieve objective response (1). An increased association of B-cell chronic lymphocytic leukemia (B-CLL) and melanoma, possibly related to an underlying immunologic defect, has been previously reported (5)...
August 22, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28826693/chimeric-antigen-receptor-t-cell-therapy-for-chronic-lymphocytic-leukemia-a-narrative-review
#14
REVIEW
Anthony R Mato, Meghan C Thompson, Chadi Nabhan, Jakub Svoboda, Stephen J Schuster
The treatment landscape for chronic lymphocytic leukemia (CLL) is changing rapidly. Novel targeted agents such as ibrutinib, venetoclax, and idelalisib have had a significant effect on first-line, relapsed/refractory, and high-risk disease. Despite these advances, there are continuous needs for new treatment options, especially for patients in whom these novel therapies fail or those who cannot tolerate these novel therapies. In 2011, Porter et al reported the first successful use of autologous chimeric antigen receptor T cells (CARTs) directed against cluster of differentiation (CD)19 in 3 refractory CLL patients...
July 21, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28810332/-study-on-the-expression-of-trip13-mrna-in-chronic-lymphocytic-leukemia-b-lymphocyte-and-the-molecular-mechanism-of-trip13-mediated-jvm-2-cell-proliferation-and-apoptosis
#15
K S Zhou, Q Zhang, W T Zhang, Y Y Liu, S S Wu, J Zhou, X D Wei, Y P Song
Objective: To investigate the clinical significance of expression level of thyroid hormone receptor interactors 13 (TRIP13) gene to probe its function and downstream molecular mechanism in chronic lymphocytic leukemia (CLL) . Methods: Real-time quantitative PCR method was used to detect the expression levels of TRIP13 mRNA of CD19(+) B lymphocytes in 30 cases of patients with CLL and 12 cases of peripheral blood hematopoietic stem cell donors (normal control group) . Lentivirus mediated shRNA was used to interference the mRNA and TRIP13 protein in CLL cells JVM-2...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28808046/car-t-cells-drive-cll-remissions
#16
(no author information available yet)
A new study shows that chimeric antigen receptor T cells produce objective responses in 71% of patients with chronic lymphocytic leukemia whose disease progressed despite receiving ibrutinib or who are unable to tolerate the drug. Cancer cells were undetectable in the bone marrow in 81% of tested patients, and 64% of tested patients showed complete lymph node responses. Most patients experienced adverse effects, however.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#17
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#18
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
September 2017: Leukemia Research
https://www.readbyqxmd.com/read/28730684/chest-wall-lymphomas-fine-needle-aspiration-cytodiagnosis-and-review-of-the-literature
#19
D K Das, S K Pathan, S K M Al-Waheeb, A E Ali, M Joneja, M G Al-Kanderi, B John, M K Mallik
OBJECTIVE: Compared to other chest wall malignancies, lymphoma is a common disease. However, published literature on a series of lymphoma cases involving the chest wall is scarce. The aim of the present study, was to describe experience with chest wall swellings diagnosed as lymphoid neoplasms on fine needle aspiration (FNA) cytology. METHODS: Eleven chest wall swellings were diagnosed as lymphoid neoplasms on FNA over a period of 15 years (January 2000-December 2014)...
July 21, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/28726646/the-prognostic-significance-of-combaind-expression-of-zap-70-and-cd38-in-chronic-lymphocytic-leukemia
#20
T Kirtava, T Vatsadze, E Azrmaiparashili, D Ghirdaladze
Our aim was to assess the inter links of the markers CD38 and ZAP-70 based on our materials, the attitude according to the disease stage, and to document which of them had leading meaning for prognosis and treatmend of the disease. In our study we have used flow cytometry for detection CD38 and ZAP-70+ markers expression. (58 patients to assessments their prognostic value in сhronic lymphocytic leukemia (CLL), Correlation to Rai stages and relationships between this markers and outcome of therapy). We divided all patients in two groups based on level of ZAP-70+ cell and CD38+cells,(I group-patients) ZAP-70+ cells <20% CD38+<30% and ZAP-70+ cells >20% and CD38>30%,(II group) becaus our in investigation shows, that ZAP -70+ is very importance independent prognoctic marker as why in ZAP-70+ cases when its number was <20%, patients had favorable prognosis - the big part of them (13(40...
June 2017: Georgian Medical News
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