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https://www.readbyqxmd.com/read/29783667/bone-marrow-defects-and-platelet-function-a-focus-on-mds-and-cll
#1
REVIEW
Sarah Luu, Elizabeth E Gardiner, Robert K Andrews
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets...
May 18, 2018: Cancers
https://www.readbyqxmd.com/read/29781323/targeting-the-b-cell-receptor-pathway-a-review-of-current-and-future-therapies-for-non-hodgkin-s-lymphoma
#2
Thomas D Rodgers, Patrick M Reagan
The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy. Areas Covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas...
May 20, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#3
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#4
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29764250/immunological-changes-with-kinase-inhibitor-therapy-for-chronic-lymphocytic-leukemia
#5
Christopher Pleyer, Adrian Wiestner, Clare Sun
Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib...
May 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29759563/targeting-the-tumor-promoting-effects-of-adenosine-in-chronic-lymphocytic-leukemia
#6
REVIEW
Yiqing Cai, Lili Feng, Xin Wang
Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29752258/how-and-when-i-do-allogeneic-transplant-in-cll
#7
John G Gribben
Allogenic stem cell transplantation (allo-SCT) has been considered the treatment of choice for high-risk patients with chronic lymphocytic leukemia (CLL) and the only approach offered with curative intent in this disease. The availability novel agents including the B cell receptor inhibitors (BCRi) ibrutinib, acalabrutinib and idelalisib, as well as venetoclax which targets the BCL2 pathway and the success of these agents in treating high-risk disease patients has made it more difficult to assess who and when in their treatment course allo-SCT should be considered...
May 11, 2018: Blood
https://www.readbyqxmd.com/read/29750316/elevated-soluble-cd23-level-indicates-increased-risk-of-b-cell-non-hodgkin-s-lymphomas-evidence-from-a-meta-analysis
#8
REVIEW
Yi-Shu Huang, Xiang Zhou, Zhi-Fang Yang, Zheng-Tao Lv
The aim of the present study was to determine whether circulating soluble CD23 (sCD23) was associated with B cells non-Hodgkin's lymphomas (B-NHL). PubMed, EMBASE, and ISI Web of Science were extensively searched without language restriction. Data was extracted in a standardized data collection sheet after two reviewers scanned studies independently. The association between sCD23 and NHL was indicated as odds ratio (OR) along with its related 95% confidence interval (95% CI). Meta-analysis was conducted via RevMan 5...
May 11, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29747654/bcl-2-as-therapeutic-target-for-hematological-malignancies
#9
REVIEW
Guilherme Fleury Perini, Glaciano Nogueira Ribeiro, Jorge Vaz Pinto Neto, Laura Tojeiro Campos, Nelson Hamerschlak
Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias...
May 11, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29742083/update-on-signal-inhibitors-in-chronic-lymphocytic-leukemia
#10
Prajwal Boddu, Nitin Jain
The last decade has seen major progress in our understanding of the pathobiology of chronic lymphocytic leukemia (CLL) and the identification of potential new therapeutic targets. As a result, researchers have developed novel targeted therapies, several of which are already approved and many of which are in advanced stages of clinical development. These new agents are much less toxic than chemoimmunotherapy and may be preferred for their superior efficacy in patients with certain high-risk features, such as del(17p)...
April 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29740389/a-rare-case-of-composite-dural-extranodal-marginal-zone-lymphoma-and-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#11
REVIEW
Mark Bustoros, Benjamin Liechty, David Zagzag, Cynthia Liu, Timothy Shepherd, Deborah Gruber, Bruce Raphael, Dimitris G Placantonakis
Background: Primary extranodal marginal zone lymphoma (MZL) of the dura is a rare neoplastic entity in the central nervous system (CNS). Methods: We used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Results: We identified 104 cases of dural MZL in the literature...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29713184/prognostic-and-clinicopathological-value-of-sirt3-expression-in-various-cancers-a-systematic-review-and-meta-analysis
#12
Yongping Zhou, Sijin Cheng, Sinuo Chen, Yongzhao Zhao
Background: Several studies have explored the prognostic value of sirtuin 3 (SIRT3) in various cancers, but obtained inconsistent results. The current systematic review and meta-analysis was conducted to investigate the association between SIRT3 expression and prognosis in various cancers. Methods: PubMed, Embase, Web of Science and the Cochrane Library were comprehensively retrieved by the end of September 29, 2017. All the relevant studies were checked and included in the meta-analysis if they met the inclusion criteria...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29709246/infections-in-patients-with-chronic-lymphocytic-leukaemia-mitigating-risk-in-the-era-of-targeted-therapies
#13
REVIEW
Benjamin W Teh, Constantine S Tam, Sasanka Handunnetti, Leon J Worth, Monica A Slavin
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection...
April 23, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29707738/central-nervous-system-localisation-of-chronic-lymphocytic-leukaemia-description-of-two-very-distinct-cases-and-a-review-of-the-literature
#14
Nyanza K L M Timmers, Josanne S de Maar, Rob C M van Kruijsdijk, Saskia K Klein
Central nervous system (CNS) localisation of chronic lymphocytic leukaemia (CLL) can induce various neurological symptoms. Unfamiliarity with this manifestation causes diagnostic delay. We present two cases of leptomeningeal CLL. These cases and our literature review emphasise that CNS localisation of CLL should be considered in patients with any neurological symptom, irrespectively of the stage and systemic activity of CLL.
April 29, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29702521/dna-damage-pathways-and-b-cell-lymphomagenesis
#15
Gero Knittel, Tim Rehkämper, Pascal Nieper, Anna Schmitt, Ruth Flümann, H Christian Reinhardt
PURPOSE OF REVIEW: Recent lymphoma genome sequencing projects have shed light on the genomic landscape of indolent and aggressive lymphomas, as well as some of the molecular mechanisms underlying recurrent mutations and translocations in these entities. Here, we review these recent genomic discoveries, focusing on acquired DNA repair defects in lymphoma. In addition, we highlight recently identified actionable molecular vulnerabilities associated with recurrent mutations in chronic lymphocytic leukemia (CLL), which serves as a model entity...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29686228/the-observed-alteration-in-bcl2-expression-following-lithium-treatment-is-influenced-by-the-choice-of-normalization-method
#16
Damri Odeya, Agam Galila, Toker Lilah
Upregulation of B-cell CLL/lymphoma (BCL)2 expression following lithium treatment is seemingly well established and has been related to the neuroprotective property of the drug. However, while demonstrated by some (but not all) studies based on low-throughput techniques (e.g. qPCR) this effect is not reflected in high-throughput studies, such as microarrays and RNAseq. This manuscript presents a systematic review of currently available reports of lithium's effect on BCL2 expression. To our surprise, we found that the majority of the literature does not support the effect of lithium on BCL2 transcript or protein levels...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29682155/targeting-mitochondrial-bioenergetics-as-a-therapeutic-strategy-for-chronic-lymphocytic-leukemia
#17
REVIEW
Subir Roy Chowdhury, Versha Banerji
Altered cellular metabolism is considered a hallmark of cancer and is fast becoming an avenue for therapeutic intervention. Mitochondria have recently been viewed as an important cellular compartment that fuels the metabolic demands of cancer cells. Mitochondria are the major source of ATP and metabolites necessary to fulfill the bioenergetics and biosynthetic demands of cancer cells. Furthermore, mitochondria are central to cell death and the main source for generation of reactive oxygen species (ROS). Overall, the growing evidence now suggests that mitochondrial bioenergetics, biogenesis, ROS production, and adaptation to intrinsic oxidative stress are elevated in chronic lymphocytic leukemia (CLL)...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29673807/frequency-and-impact-of-grade-three-or-four-toxicities-of-novel-agents-on-outcomes-of-older-patients-with-chronic-lymphocytic-leukemia-and-non-hodgkin-lymphoma-alliance-a151611
#18
Michael Tallarico, Jared C Foster, Drew Seisler, Jacqueline M Lafky, Arti Hurria, Aminah Jatoi, Harvey J Cohen, Hyman B Muss, Nancy Bartlett, Bruce D Cheson, Sin-Ho Jung, John P Leonard, John C Byrd, Chadi Nabhan
OBJECTIVE: Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. PATIENTS AND METHODS: We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014...
April 16, 2018: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/29670635/chronic-lymphocytic-leukemia-b-cell-normal-cellular-counterpart-clues-from-a-functional-perspective
#19
REVIEW
Walaa Darwiche, Brigitte Gubler, Jean-Pierre Marolleau, Hussein Ghamlouch
Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669600/review-of-targeted-therapy-in-chronic-lymphocytic-leukemia-what-a-radiologist-needs-to-know-about-ct-interpretation
#20
REVIEW
Babina Gosangi, Matthew Davids, Bhanusupriya Somarouthu, Francesco Alessandrino, Angela Giardino, Nikhil Ramaiya, Katherine Krajewski
The last 5 years have been marked by profound innovation in the targeted treatment of chronic lymphocytic leukemia (CLL) and indolent lymphomas. Using CLL as a case study, we present a timeline and overview of the current treatment landscape for the radiologist, including an overview of clinical and radiological features of CLL, discussion of the targeted agents themselves, and the role of imaging in response and toxicity assessment. The goal is to familiarize the radiologist with multiple Food and Drug Administration (FDA)-approved targeted agents used in this setting and associated adverse events which are commonly observed in this patient population...
April 18, 2018: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
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