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https://www.readbyqxmd.com/read/28644154/acute-promyelocytic-leukemia-and-chronic-lymphocytic-leukemia-concomitant-presentation-of-two-molecularly-distinct-entities
#1
Jingdong Su, Diana Veillon, Rodney Shackelford, James Cotelingam, Hazem El-Osta, Glenn Mills, Reinhold Munker, Srinivas Devarakonda
Acute myeloid leukemia (AML) developing in patients with chronic lymphocytic leukemia (CLL) is very uncommon and usually associated with prior treatment. Acute promyelocytic leukemia (APL) accounts for a very small proportion of treatment-associated AML. So far, there has been only one reported case of APL occurring post radiation for prostate cancer in a patient with CLL. We report herein the first case of APL and CLL presenting concomitantly in an untreated patient. Evaluation of peripheral blood and bone marrow aspirate with immunohistochemistry, flow cytometry, and FISH to confirm two morphologically, molecularly and genetically distinct leukemic populations characteristic of APL and CLL is required...
May 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28641468/association-between-immunoglobulin-heavy-chain-variable-region-mutational-status-and-isolated-favorable-baseline-genomic-aberrations-in-chronic-lymphocytic-leukemia
#2
Jose D Sandoval-Sus, Julio C Chavez, Samir Dalia, Syeda Mahrukh Hussnain Naqvi, Chetasi Talati, Lisa Nodzon, Mohamed A Kharfan-Dabaja, Javier Pinilla-Ibarz
Immunoglobulin heavy-chain variable region (IGHV) mutational status and karyotype abnormalities are important prognostic factors in chronic lymphocytic leukemia (CLL). The goal was to assess the impact of IGHV in CLL patients with isolated favorable genetic aberrations (del13q, trisomy 12, or negative fluorescence in situ hybridization [FISH]). We studied 273 CLL patients with both IGHV mutational status and cytogenetic information: 145 with isolated del13q 49 with sole trisomy 12 and 79 with negative FISH...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28639485/increased-shisa3-expression-characterizes-chronic-lymphocytic-leukemia-patients-sensitive-to-lenalidomide
#3
Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Jenny Bulgarelli, Lara Rizzotto, Giulia Debbia, Rita Santachiara, Gian Matteo Rigolin, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca
Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28632812/systemic-interferon-alfa-injections-for-the-treatment-of-a-giant-orf
#4
Sumeyre Seda Ertekin, Mehmet Salih Gurel, Aslı Vefa Turgut Erdemir, Cem Leblebici
Orf is a zoonotic infection caused by a parapoxvirus and is endemic in sheep and goats. It may be transmitted to humans by direct contact with infected animals. We report a case of a giant orf in a patient with chronic lymphocytic leukemia (CLL), which proliferated dramatically after surgical excision and resolved after systemic interferon alfa-2a injections.
May 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28628003/clinical-effectiveness-and-cost-effectiveness-results-from-the-randomised-phase-iib-trial-in-previously-untreated-patients-with-chronic-lymphocytic-leukaemia-to-compare-fludarabine-cyclophosphamide-and-rituximab-with-fludarabine-cyclophosphamide-mitoxantrone
#5
Dena R Howard, Talha Munir, Lucy McParland, Andy C Rawstron, Anna Chalmers, Walter M Gregory, John L O'Dwyer, Alison Smith, Roberta Longo, Abraham Varghese, Alexandra Smith, Peter Hillmen
BACKGROUND: The conventional frontline therapy for fit patients with chronic lymphocytic leukaemia (CLL) is fludarabine, cyclophosphamide and rituximab (FCR). Rituximab (Mabthera(®), Roche Products Ltd) targets the CD20 antigen, which is expressed at low levels in CLL. The standard dose of rituximab in CLL (375 mg/m(2) in cycle 1 and 500 mg/m(2) in cycles 2-6) was selected based on toxicity data only. Small doses of rituximab (as low as 20 mg) have biological activity in CLL, with an immediate reduction in circulating CLL cells and down-regulation of CD20...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28627951/the-safety-of-bruton-s-tyrosine-kinase-inhibitors-for-the-treatment-of-chronic-lymphocytic-leukemia
#6
Phu N Tran, Susan O'Brien
The approval of ibrutinib has revolutionized the therapeutic landscape of chronic lymphocytic leukemia (CLL). Currently ibrutinib is indicated for patients that are both treatment naïve as well as those with relapsed CLL. Ibrutinib is generally well-tolerated with durable responses that improve over time in most patients. Important toxicities include atrial fibrillation and bleeding. Areas Cover: This review covers the pharmacokinetics, pharmacodynamics, safety and efficacy of ibrutinib in the treatment of CLL...
June 19, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#7
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28614781/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#8
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/28605616/managing-patients-with-tp53-deficient-chronic-lymphocytic-leukemia
#9
Jennifer Edelmann, John G Gribben
Patients with chronic lymphocytic leukemia (CLL) having a chromosomal loss on the short arm of chromosome 17 including the TP53 gene locus (17p deletion) and/or having mutations in TP53 have a short overall survival and, until recently, limited treatment options. The recent introduction of two novel substance classes, B-cell receptor inhibitors and BH3 mimetics, into CLL treatment has provided enormous clinical progress in this previously difficult-to-treat patient subgroup characterized by high risk for treatment failure with standard chemoimmunotherapy and rapid disease progression...
June 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28604954/-detection-of-genomic-abnormalities-among-105-patients-with-chronic-lymphocytic-leukemia-using-fluorescence-in-situ-hybridization
#10
Huanping Wang, Huan Xu, Zhimei Chen, Jiyu Lou, Jie Jin
OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) for the detection of genomic abnormalities among patients with chronic lymphocytic leukemia (CLL). METHODS: Interphase FISH was performed on bone marrow samples derived from 105 patients with CLL at the time of diagnosis using probes for D13S319/13q14, ATM/11q22, P53/17p13 and CEP12. The abnormalities and prognostic factors were analyzed. Overall survival of the patients was calculated. RESULTS: The FISH assay has detected genomic abnormalities in 81 (77...
June 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28603911/cd11c-expression-in-chronic-lymphocytic-leukemia-revisited-related-with-complications-and-survival
#11
E G Umit, M Baysal, Y Durmus, A M Demir
INTRODUCTION: Chronic lymphocytic leukemia (CLL) is a disorder of mature but dysfunctional monoclonal B cells. Microenvironment, antigenic stimulation and genetical mutations are demonstrated in etiopathogenesis. We aimed to evaluate the expression of CD11c in patients with CLL and its possible clinical significance. METHODS: Data of 259 patients with CLL between 2010 and 2016 in Trakya University Faculty of Medicine, including age at diagnosis, sex, whole blood count, stage, percentage of CLL cells in bone marrow, line of treatments, development of Richter's transformation and secondary tumors, autoimmune complications, IgG level, prognostic cytogenetic analysis, and length of survival were recorded from files...
June 12, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28600336/diagnosis-and-classification-of-hematologic-malignancies-on-the-basis-of-genetics
#12
Justin Taylor, Wenbin Xiao, Omar Abdel-Wahab
Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia...
June 9, 2017: Blood
https://www.readbyqxmd.com/read/28599315/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#13
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28599250/evaluation-of-mir-15a-and-mir-16-1-as-prognostic-biomarkers-in-chronic-lymphocytic-leukemia
#14
REVIEW
Tatiane Vieira Braga, Fernanda Cristina Gontijo Evangelista, Lorena Caixeta Gomes, Sérgio Schusterschitz da Silva Araújo, Maria das Graças Carvalho, Adriano de Paula Sabino
Chronic lymphocytic leukemia (CLL) is a B lineage neoplasm, characterized by the accumulation of B lymphocytes of great longevity, and usually develops as a result of the inhibition of apoptosis. Clinical evolution is extremely variable amongst affected individuals with survival ranging from a few months in aggressive cases, to a few decades in cases of indolent CLL. The identification of new prognostic factors, apart from clinical staging, has been an important research topic aiming at a better understanding of CLL...
June 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28598442/distinct-homotypic-b-cell-receptor-interactions-shape-the-outcome-of-chronic-lymphocytic-leukaemia
#15
Claudia Minici, Maria Gounari, Rudolf Übelhart, Lydia Scarfò, Marcus Dühren-von Minden, Dunja Schneider, Alpaslan Tasdogan, Alabbas Alkhatib, Andreas Agathangelidis, Stavroula Ntoufa, Nicholas Chiorazzi, Hassan Jumaa, Kostas Stamatopoulos, Paolo Ghia, Massimo Degano
Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR-BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28596506/by-up-regulating-%C3%AE-and-%C3%AE-opioid-receptors-neuron-restrictive-silencer-factor-knockdown-promotes-neurological-recovery-after-ischemia
#16
Hui-Min Liang, Li-Jiao Geng, Xiao-Yan Shi, Chao-Gang Zhang, Shu-Yan Wang, Guang-Ming Zhang
We investigated the effects of neuron-restrictive silencer factor (NRSF) on proliferation of endogenous nerve stem cells (NSCs) and on μ- and δ-opioid receptor (MOR/DOR) expression in rats after cerebral ischemia. Among 100 rats subjected to cerebral ischemia, 20 rats were transfected with NRSF shRNA, and the remaining 80 were randomly assigned to normal, sham, model, and negative control (NC) groups. On days 7, 14, and 28 after ischemia and reperfusion, neurological function scores were assigned and a step-down passive avoidance test was conducted...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596424/s100-a9-protein-in-exosomes-from-chronic-lymphocytic-leukemia-cells-promotes-nf-%C3%AE%C2%BAb-activity-during-disease-progression
#17
Daniel Prieto, Natalia Sotelo, Noé Seija, Sandra Sernbo, Cecilia Abreu, Rosario Durán, Magdalena Gil, Estefanía Sicco, Victoria Irigoin, Carolina Oliver, Ana Inés Landoni, Raúl Gabus, Guillermo Dighiero, Pablo Oppezzo
Chronic Lymphocytic Leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. A continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of the exosomes are altered as tumors progress to an aggressive phenotype...
June 8, 2017: Blood
https://www.readbyqxmd.com/read/28592889/extended-follow-up-and-impact-of-high-risk-prognostic-factors-from-the-phase-3-resonate-tm-study-in-patients-with-previously-treated-cll-sll
#18
J R Brown, P Hillmen, S O'Brien, J C Barrientos, N M Reddy, S E Coutre, C S Tam, S P Mulligan, U Jaeger, P M Barr, R R Furman, T J Kipps, F Cymbalista, P Thornton, F Caligaris-Cappio, J Delgado, M Montillo, S DeVos, C Moreno, J M Pagel, T Munir, J A Burger, D Chung, J Lin, L Gau, B Chang, G Cole, E Hsu, D F James, J C Byrd
In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%)...
June 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28592762/chronic-lymphocytic-leukemia-pathophysiology-and-current-therapy
#19
Jun Takizawa
Chronic lymphocytic leukemia (CLL) is the most frequent adult leukemia in western countries, but it is rare in Japan. Several mutations have been identified in patients with CLL using next-generation sequencing, but disease-specific mutations were not found. Some mutations, such as those in TP53, NOTCH1, SF3B, and BIRC3 are useful for risk stratification and prognosis prediction in patients with CLL. Strategies for treating CLL are rapidly evolving, with targeted agents such as the B-cell receptor signaling pathway inhibitors (ibrutinib, idelalisib), novel anti-CD20 monoclonal antibody (obinutuzumab), and Bcl-2 inhibitor (venetoclax) being approved by the US Food and Drug Administration...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28591418/role-and-timing-of-new-drugs-in-cll
#20
Michael Hallek
No abstract text is available yet for this article.
June 2017: Hematological Oncology
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