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https://www.readbyqxmd.com/read/27872727/identifying-high-risk-chronic-lymphocytic-leukemia-a-pathogenesis-oriented-appraisal-of-prognostic-and-predictive-factors-in-patients-treated-with-chemotherapy-with-or-without-immunotherapy
#1
REVIEW
Sara Martinelli, Antonio Cuneo, Luca Formigaro, Maurizio Cavallari, Enrico Lista, Francesca Maria Quaglia, Maria Ciccone, Antonella Bardi, Eleonora Volta, Elisa Tammiso, Elena Saccenti, Olga Sofritti, Giulia Daghia, Massimo Negrini, Melissa Dabusti, Paolo Tomasi, Sabrina Moretti, Francesco Cavazzini, Gian Matteo Rigolin
Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#2
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27833611/activated-allogeneic-nk-cells-preferentially-kill-poor-prognosis-b-cell-chronic-lymphocytic-leukemia-cells
#3
Diego Sánchez-Martínez, Pilar M Lanuza, Natalia Gómez, Aura Muntasell, Elisa Cisneros, Manuela Moraru, Gemma Azaceta, Alberto Anel, Luis Martínez-Lostao, Martin Villalba, Luis Palomera, Carlos Vilches, José A García Marco, Julián Pardo
Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27808579/predictive-and-prognostic-biomarkers-in-the-era-of-new-targeted-therapies-for-chronic-lymphocytic-leukemia
#4
Davide Rossi, Bernhard Gerber, Georg Stüssi
Treatment options for chronic lymphocytic leukemia (CLL) have improved with the introduction of the B-cell receptor inhibitors ibrutinib and idelalisib, and of the BCL2 inhibitor venetoclax. While awaiting the results of head to head comparisons between novel agents and chemoimmunotherapy, predictive biomarkers can assist physicians in treatment tailoring. Though novel agents have modified the landscape of predictors at the time of treatment requirement, the usefulness of historical CLL prognostic biomarkers is still up-to-date when considering anticipation of time to first treatment...
November 3, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27803007/management-of-chronic-lymphocytic-leukemia-cll-in-the-elderly-a-position-paper-from-an-international-society-of-geriatric-oncology-siog-task-force
#5
REVIEW
R Stauder, B Eichhorst, M Hamaker, K Kaplanov, V Morrison, A Österborg, I Poddubnaya, J A Woyach, T Shanafelt, L Smolej, L Ysebaert, V Goede
Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is above seventy years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living, and social support...
November 1, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27761889/microrna-155-in-serum-derived-extracellular-vesicles-as-a-potential-biomarker-for-hematologic-malignancies-a-short-report
#6
Antonella Caivano, Francesco La Rocca, Vittorio Simeon, Marco Girasole, Simone Dinarelli, Ilaria Laurenzana, Angelo De Stradis, Luciana De Luca, Stefania Trino, Antonio Traficante, Giovanni D'Arena, Giovanna Mansueto, Oreste Villani, Giuseppe Pietrantuono, Luca Laurenti, Luigi Del Vecchio, Pellegrino Musto
PURPOSE: The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported...
October 19, 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27742074/biomarkers-in-chronic-lymphocytic-leukemia-clinical-applications-and-prognostic-markers
#7
Carlos I Amaya-Chanaga, Laura Z Rassenti
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The Rai and Binet staging systems are often used to predict survival. However, they do not take into account other biological characteristics of CLL cells that may influence the disease course and response to treatment. Prognostic factors such as chromosome abnormalities (trisomy 12, 11q deletions and 17p deletions), β2 microglobulin, thymidine kinase, CD38 and ZAP-70 expression, IGHV mutation status, and mutations in genes such as NOTCH1, MYD88, SF3B1, and ATM are also predictors of prognosis...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27742064/present-and-future-of-personalized-medicine-in-cll
#8
Emili Montserrat, Tycho Bauman, Julio Delgado
Medicine has been 'personalized' (i.e. centred in persons) since its foundation. Recently, however, the term 'personalized medicine' (or, better, 'precision medicine') has been introduced to define 'a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease'. This concept has gained momentum thanks to next-generation-sequencing (NGS) techniques that allow identification of molecular characteristics unique to the patient and to the tumour...
March 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27739922/characterization-and-prognostic-relevance-of-circulating-microvesicles-in-chronic-lymphocytic-leukemia
#9
Luciana De Luca, Giovanni D'Arena, Vittorio Simeon, Stefania Trino, Ilaria Laurenzana, Antonella Caivano, Francesco La Rocca, Oreste Villani, Giovanna Mansueto, Silvia Deaglio, Idanna Innocenti, Luca Laurenti, Stefano Molica, Giuseppe Pietrantuono, Angelo De Stradis, Luigi Del Vecchio, Pellegrino Musto
Microvescicles (MV) are shedding particles released by normal and neoplastic cells, whose levels in biological fluids highlight their potential role as disease biomarkers and therapeutic targets. By analyzing 131 newly diagnosed chronic lymphocytic leukemia (CLL), we found that the absolute number of serum CLL MV was significantly higher than in controls, in particular in advanced stages of disease. In addition, CD19 + and CD37+, B-cell derived MV, significantly correlated with high tumor burden. Absolute MV number cutoff selected by ROC analysis distinguished Rai stage 0 patients with shorter time to treatment (TTT) from those with more stable disease...
October 14, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27659777/circulating-microrna-192-as-a-diagnostic-biomarker-in-human-chronic-lymphocytic-leukemia
#10
S Fathullahzadeh, H Mirzaei, M A Honardoost, A Sahebkar, M Salehi
Chronic lymphocytic leukemia (CLL) is known as the most common lymphoid malignancy in the Western world. MicroRNAs (miRNAs) are a class of small noncoding RNAs with pivotal roles in cellular and molecular processes related to different malignancies including CLL. Recently, some studies have shown that miR-192 plays a key role in CLL pathogenesis through increasing CDKN1A/p21 levels, suppression of Bcl-2 and enhancement of wild-type P53 and cell cycle arrest. Forty samples, including 20 patients with CLL, diagnosed in Omid hospital (Isfahan, Iran) and 20 healthy controls were sampled during a period of 4 months...
September 23, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27572553/microrna-19b-inhibits-proliferation-of-gastric-cancer-cells-by-targeting-b-cell-cll-lymphoma-3
#11
Huan Wang, Mei Xiong, Yongwu Hu, Yusheng Sun, Qing Ma
Previous studies reported that the aberrant expression of miR-19b in gastric cancer tissues and circulating miR-19b is a potential biomarker to indicate progression of gastric cancer. However, the prognostic significance of miR-19b, and its role and underlying mechanisms in gastric cancer remain poorly investigated. In the present study, we demonstrated that the expression of miR-19b was aberrantly downregulated in both gastric cancer tissues and cell lines. Clinical association analyses disclosed that the reduced expression of miR-19b was significantly associated with adverse clinicopathological characteristics including poor differentiation, large tumor size and advanced tumor-node-metastasis (TNM) stage...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27569460/-extracellular-vesicles-and-their-role-in-hematological-malignancies
#12
Andrea Rzepiel, Nóra Kutszegi, Judit Cs Sági, Andrea Kelemen, Krisztina Pálóczi, Ágnes F Semsei, Edit Buzás, Dániel János Erdélyi
Extracellular vesicles are produced in all organisms. The most intensively investigated categories of extracellular vesicles include apoptotic bodies, microvesicles and exosomes. Among a very wide range of areas, their role has been confirmed in intercellular communication, immune response and angiogenesis (in both physiological and pathological conditions). Their alterations suggest the potential use of them as biomarkers. In this paper the authors give an insight into the research of extracellular vesicles in general, and then focus on published findings in hematological malignancies...
August 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27557899/microrna-epigenetic-signatures-in-human-disease
#13
REVIEW
Klara Piletič, Tanja Kunej
MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene...
October 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27521330/treatment-of-chronic-lymphocytic-leukemia-with-del-17p-tp53-mutation-allogeneic-hematopoietic-stem-cell-transplantation-or-bcr-signaling-inhibitors
#14
REVIEW
Emili Montserrat, Peter Dreger
The treatment of patients with chronic lymphocytic leukemia (CLL) whose tumor presents the del(17p)/TP53 mutation is a major challenge. Treatment with chemo(immuno)therapy, immunomodulators, or the anti-CD52 monoclonal antibody alemtuzumab produces transient, unsatisfactory responses. Reduced-intensity-conditioning allotransplantation produces sustained progression-free survival and overall survival (40%-60% at 5 years), equivalent to the cure of the disease, even in cases with adverse biomarkers. Unfortunately, despite improvements in this procedure, the non-relapse mortality continues to be high (15%-30%), and only highly selected patients (young, physically fit, with treatment-sensitive disease, not heavily pretreated, and with a fully matched donor) may benefit from the intervention without incurring unacceptable treatment-related risks...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27499136/hox-gene-expression-predicts-response-to-bcl-2-inhibition-in-acute-myeloid-leukemia
#15
M Kontro, A Kumar, M M Majumder, S Eldfors, A Parsons, T Pemovska, J Saarela, B Yadav, D Malani, Y Fløisand, M Höglund, K Remes, B T Gjertsen, O Kallioniemi, K Wennerberg, C A Heckman, K Porkka
Inhibitors of BCL-2 such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, then comprehensively assessed if the responses correlated to specific mutations or gene expression signatures. Compared to samples from healthy donor controls (non-sensitive) and chronic lymphocytic leukemia (CLL) patients (highly-sensitive), AML samples exhibited variable responses to BCL-2 inhibition...
August 8, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27486974/telomere-status-in-chronic-lymphocytic-leukemia-with-tp53-disruption
#16
Romain Guièze, Mélanie Pages, Lauren Véronèse, Patricia Combes, Richard Lemal, Mathilde Gay-Bellile, Martine Chauvet, Mary Callanan, Fabrice Kwiatkowski, Bruno Pereira, Philippe Vago, Jacques-Olivier Bay, Olivier Tournilhac, Andreï Tchirkov
In chronic lymphocytic leukemia (CLL), telomere dysfunction is associated with poor outcomes. TP53 is involved in cellular responses to dysfunctional telomeres, and its inactivation is the strongest adverse prognostic factor for CLL. Given the biological relationship between TP53 and telomeres, and their prognostic value, it is important to improve our understanding of the impact of TP53 alterations on telomeres. We performed a comprehensive study of the deletions and mutations of the TP53 gene and telomere parameters, including hTERT and the shelterin complex, in 115 CLL patients...
July 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27480387/dynamics-of-microvesicle-generation-in-b-cell-chronic-lymphocytic-leukemia-implication-in-disease-progression
#17
J Boysen, M Nelson, G Magzoub, G P Maiti, S Sinha, M Goswami, S K Vesely, T D Shanafelt, N E Kay, A K Ghosh
Previously, we reported that B-cell chronic lymphocytic leukemia (CLL) patients contained elevated levels of microvesicles (MVs). However, given the quiescent nature of CLL B-cells and the relative indolence of the disease, the dynamics of MV generation and their unique phenotypes are not clearly defined. In this study, we find that CLL B-cells generate MVs spontaneously and can be further induced by B-cell receptor-ligation. Most interestingly, CLL B-cells predominantly generate CD52(+) MVs, but not CD19(+) MVs in vitro, suggesting preferential usage of CD52 into leukemic-MVs and that the CLL plasma MV phenotypes corroborate well with the in vitro findings...
August 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27476172/different-expression-levels-of-glycans-on-leukemic-cells-a-novel-screening-method-with-molecularly-imprinted-polymers-mip-targeting-sialic-acid
#18
Zahra El-Schich, Mohammad Abdullah, Sudhirkumar Shinde, Nishtman Dizeyi, Anders Rosén, Börje Sellergren, Anette Gjörloff Wingren
Sialic acid (SA) is normally expressed on the cell membranes and is located at the terminal position of the sugar chains. SA plays an important role for regulation of the innate immunity, function as markers of the cells and can be recognized by a variety of receptors. Interestingly, the level of SA expression is increased on metastatic cancer cells. The availability of specific antibodies against SA is limited and, therefore, biomarker tools for detection of SA are lacking. We have recently presented a novel method for specific fluorescence labeling of SA molecular imprinted polymers (MIP)...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27414262/histologic-transformation-of-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#19
REVIEW
Rose Lou Marie C Agbay, Nitin Jain, Sanam Loghavi, L Jeffrey Medeiros, Joseph D Khoury
Although generally considered a clinically indolent neoplasm, CLL/SLL may undergo transformation to a clinically aggressive lymphoma. The most common form of transformation, to DLBCL, is also known as Richter syndrome. Transformation determines the course of the disease and is associated with unfavorable patient outcome. Precise detection of transformation and identification of predictive biomarkers and specific molecular pathways implicated in the pathobiology of transformation in CLL/SLL will enable personalized therapeutic approach and provide potential avenues for improving the clinical outcome of patients...
October 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27317602/adipose-tissue-biomarkers-involved-in-early-resolution-of-type-2-diabetes-after-bariatric-surgery
#20
Lourdes Garrido-Sánchez, Monica Tomé, Concepcion Santiago-Fernández, Sara García-Serrano, Eduardo García-Fuentes, Francisco J Tinahones
BACKGROUND: Bariatric surgery improves glycemic metabolism, even before weight loss. However, this improvement in carbohydrate metabolism is not always sufficient for complete remission of type 2 diabetes (T2D). The previous inflammatory state of the adipose tissue may affect this improvement. OBJECTIVES: We assessed whether the gene expression of inflammatory markers in visceral adipose tissue and subcutaneous adipose tissue (SAT) was associated with the short-term remission of T2D after bariatric surgery...
March 16, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
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