Author
Mark Liebow
Other affiliations: American College of Physicians
Bio: Mark Liebow is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Single-nucleotide polymorphism & Follicular lymphoma. The author has an hindex of 30, co-authored 66 publications receiving 3046 citations. Previous affiliations of Mark Liebow include American College of Physicians.
Papers published on a yearly basis
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National Institutes of Health1, Mayo Clinic2, City of Hope National Medical Center3, University of New South Wales4, University of Alabama5, University of California, San Francisco6, Karolinska Institutet7, University of Chicago8, Yale University9, University of Bordeaux10, Macquarie University11, University of Paris-Sud12, Harvard University13, Stanford University14, Exponent15, Uppsala University16, Statens Serum Institut17, University of Florence18, Imperial College London19, German Cancer Research Center20, Icahn School of Medicine at Mount Sinai21, International Agency for Research on Cancer22, University of Cagliari23, University of Burgundy24, University of Freiburg25, Dublin City University26, University of Southern California27, University of Washington28, Fred Hutchinson Cancer Research Center29, Drexel University30, Wayne State University31, University of York32, Simon Fraser University33, University of British Columbia34, University of Sydney35, University of Milan36, Mario Negri Institute for Pharmacological Research37, University of Rochester38, Cancer Prevention Institute of California39, Emory University40, Boston University41, Roger Williams Medical Center42
TL;DR: Using a novel approach to investigate etiologic heterogeneity among NHL subtypes,risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes are identified, suggesting both subtype-specific and shared underlying mechanisms.
Abstract: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the fifth most common type of cancer in more developed regions of the world (1). Numerous NHL subtypes with distinct combinations of morphologic, immunophenotypic, genetic, and clinical features are currently recognized (2,3). The incidence of NHL subtypes varies substantially by age, sex, and race/ethnicity (4–7). However, the etiological implications of this biological, clinical, and epidemiological diversity are incompletely understood.
The importance of investigating etiology by NHL subtype is clearly supported by research on immunosuppression, infections, and autoimmune diseases, which are the strongest and most established risk factors for NHL. Studies of solid organ transplant recipients and individuals infected with HIV demonstrate that risks are markedly increased for several—but not all—NHL subtypes (8–13). Some infections and autoimmune diseases are associated with a single specific subtype [eg, human T-cell lymphotropic virus, type I (HTLV-I) with adult T-cell leukemia/lymphoma (14), celiac disease with enteropathy-type peripheral T-cell lymphoma (PTCL) (15–17)], whereas others [eg, Epstein–Barr virus, hepatitis C virus (HCV), Sjogren’s syndrome (18–21)] have been associated with multiple subtypes.
In the last two decades, reports from individual epidemiological studies of NHL have suggested differences in risks among NHL subtypes for a wide range of risk factors, but most studies have lacked the statistical power to assess any differences quantitatively and have not systematically evaluated combinations of subtypes. One study assessed multiple risk factors and found support for both etiologic commonality and heterogeneity for NHL subtypes, with risk factor patterns suggesting that immune dysfunction is of greater etiologic importance for diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma than for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (22). However, that analysis was limited to approximately 1300 NHL cases and considered only the four most common NHL subtypes. Pooling data from multiple studies through the International Lymphoma Epidemiology Consortium (InterLymph) have provided substantial insight into associations between specific risk factors and NHL subtypes, with evidence that family history of hematologic malignancy, autoimmune diseases, atopic conditions, lifestyle factors (smoking, alcohol, anthropometric measures, and hair dye use), and sun exposure are associated with NHL risk (19,21,23–32). However, no previous study has compared patterns of risk for a range of exposures for both common and rarer NHL subtypes.
We undertook the InterLymph NHL Subtypes Project, a pooled analysis of 20 case–control studies including 17 471 NHL cases and 23 096 controls, to advance understanding of NHL etiology by investigating NHL subtype-specific risks associated with medical history, family history of hematologic malignancy, lifestyle factors, and occupation. The detailed risk factor profiles for each of 11 NHL subtypes appear in this issue (15–17,33–40). In this report, we assess risk factor heterogeneity among the NHL subtypes and identify subtypes that have similar risk factor profiles.
273 citations
TL;DR: In this survey about health care cost containment, US physicians reported having some responsibility to address health care costs in their practice and expressed general agreement about several quality initiatives to reduce cost but reported less enthusiasm for cost containment involving changes in payment models.
Abstract: Importance Physicians’ views about health care costs are germane to pending policy reforms. Objective To assess physicians’ attitudes toward and perceived role in addressing health care costs. Design, Setting, and Participants A cross-sectional survey mailed in 2012 to 3897 US physicians randomly selected from the AMA Masterfile. Main Outcomes and Measures Enthusiasm for 17 cost-containment strategies and agreement with an 11-measure cost-consciousness scale. Results A total of 2556 physicians responded (response rate = 65%). Most believed that trial lawyers (60%), health insurance companies (59%), hospitals and health systems (56%), pharmaceutical and device manufacturers (56%), and patients (52%) have a “major responsibility” for reducing health care costs, whereas only 36% reported that practicing physicians have “major responsibility.” Most were “very enthusiastic” for “promoting continuity of care” (75%), “expanding access to quality and safety data” (51%), and “limiting access to expensive treatments with little net benefit” (51%) as a means of reducing health care costs. Few expressed enthusiasm for “eliminating fee-for-service payment models” (7%). Most physicians reported being “aware of the costs of the tests/treatments [they] recommend” (76%), agreed they should adhere to clinical guidelines that discourage the use of marginally beneficial care (79%), and agreed that they “should be solely devoted to individual patients’ best interests, even if that is expensive” (78%) and that “doctors need to take a more prominent role in limiting use of unnecessary tests” (89%). Most (85%) disagreed that they “should sometimes deny beneficial but costly services to certain patients because resources should go to other patients that need them more.” In multivariable logistic regression models testing associations with enthusiasm for key cost-containment strategies, having a salary plus bonus or salary-only compensation type was independently associated with enthusiasm for “eliminating fee for service” (salary plus bonus: odds ratio [OR], 3.3, 99% CI, 1.8-6.1; salary only: OR, 4.3, 99% CI, 2.2-8.5). In multivariable linear regression models, group or government practice setting (β = 0.87, 95% CI, 0.29 to 1.45, P = .004; and β = 0.99, 95% CI, 0.20 to 1.79, P = .01, respectively) and having a salary plus bonus compensation type (β = 0.82; 95% CI, 0.32 to 1.33; P = .002) were positively associated with cost-consciousness. Finding the “uncertainty involved in patient care disconcerting” was negatively associated with cost-consciousness (β = −1.95; 95% CI, −2.71 to −1.18; P Conclusion and Relevance In this survey about health care cost containment, US physicians reported having some responsibility to address health care costs in their practice and expressed general agreement about several quality initiatives to reduce cost but reported less enthusiasm for cost containment involving changes in payment models.
221 citations
National Institutes of Health1, University of California, Berkeley2, University of Alabama3, Memorial Sloan Kettering Cancer Center4, University of Utah5, University of Freiburg6, University of Southern California7, French Institute of Health and Medical Research8, City of Hope National Medical Center9, Imperial College London10, American Cancer Society11, University of British Columbia12, Simon Fraser University13, Harvard University14, University of Sydney15, University of Cagliari16, Yale University17, Cancer Council Victoria18, New York University19, Mayo Clinic20, Karolinska Institutet21, Statens Serum Institut22, Uppsala University23, Stanford University24, Exponent25, Veterans Health Administration26, University of Iowa27, University of California, San Francisco28, Ohio State University29, Fred Hutchinson Cancer Research Center30, German Cancer Research Center31, Icahn School of Medicine at Mount Sinai32, International Agency for Research on Cancer33, University of Burgundy34, Dublin City University35, University of Texas MD Anderson Cancer Center36, Duke University37, University of Minnesota38, Wayne State University39, Academy of Athens40, Utrecht University41, University of Oxford42, National Institute for Health and Welfare43, Macquarie University44, University of New South Wales45, University of Bari46, University of York47, Dongguk University48, University of North Carolina at Chapel Hill49, University of Sheffield50, University of Santiago de Compostela51, University of Oviedo52, University of Barcelona53
TL;DR: The largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls, identified ten independent associated SNPs in nine new loci and found evidence for two additional promising loci below genome-wide significance.
Abstract: Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
202 citations
01 Sep 2013
TL;DR: The design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank are reported, demonstrating that the biobank has quickly been established as a valuable resource for researchers.
Abstract: Objective To report the design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank. Patients and Methods Preparations for this biobank began with a 4-day Deliberative Community Engagement with local residents to obtain community input into the design and governance of the biobank. Recruitment, which began in April 2009, is ongoing, with a target goal of 50,000. Any Mayo Clinic patient who is 18 years or older, able to consent, and a US resident is eligible to participate. Each participant completes a health history questionnaire, provides a blood sample, and allows access to existing tissue specimens and all data from their Mayo Clinic electronic medical record. A community advisory board provides ongoing advice and guidance on complex decisions. Results After 3 years of recruitment, 21,736 individuals have enrolled. Fifty-eight percent (12,498) of participants are female and 95% (20,541) of European ancestry. Median participant age is 62 years. Seventy-four percent (16,171) live in Minnesota, with 42% (9157) from Olmsted County, where the Mayo Clinic in Rochester, Minnesota, is located. The 5 most commonly self-reported conditions are hyperlipidemia (8979, 41%), hypertension (8174, 38%), osteoarthritis (6448, 30%), any cancer (6224, 29%), and gastroesophageal reflux disease (5669, 26%). Among patients with self-reported cancer, the 5 most common types are nonmelanoma skin cancer (2950, 14%), prostate cancer (1107, 12% in men), breast cancer (941, 4%), melanoma (692, 3%), and cervical cancer (240, 2% in women). Fifty-six percent (12,115) of participants have at least 15 years of electronic medical record history. To date, more than 60 projects and more than 69,000 samples have been approved for use. Conclusion The Mayo Clinic Biobank has quickly been established as a valuable resource for researchers.
174 citations
TL;DR: Spending on health care in the United States has been rising at a faster pace than spending in the rest of the economy since the 1960s and is expected to reach $4.0 trillion and amount to 20% of the GDP by 2015.
Abstract: This position paper concerns improving health care in the United States. Unlike previous highly focused policy papers by the American College of Physicians, this article takes a comprehensive approach to improving access, quality, and efficiency of care. The first part describes health care in the United States. The second compares it with health care in other countries. The concluding section proposes lessons that the United States can learn from these countries and recommendations for achieving a high-performance health care system in the United States. The articles are based on a position paper developed by the American College of Physicians' Health and Public Policy Committee. This policy paper (not included in this article) also provides a detailed analysis of health care systems in 12 other industrialized countries. Although we can learn much from other health systems, the College recognizes that our political and social culture, demographics, and form of government will shape any solution for the United States. This caution notwithstanding, we have identified several approaches that have worked well for countries like ours and could probably be adapted to the unique circumstances in the United States.
159 citations
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29 Sep 2017
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Abstract: WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
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Massachusetts Institute of Technology1, Broad Institute2, University of California, Los Angeles3, University of British Columbia4, Baylor College of Medicine5, Howard Hughes Medical Institute6, University of Washington7, Ludwig Institute for Cancer Research8, University of California, San Francisco9, University of Connecticut10, University of Zagreb11, University of Texas at Austin12, Washington University in St. Louis13, University of Queensland14, Harvard University15, Cold Spring Harbor Laboratory16, University of Southern California17, University of California, Santa Cruz18, Simon Fraser University19, Morgridge Institute for Research20, University of Texas at Dallas21, National Institutes of Health22
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
5,037 citations
01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
4,409 citations
TL;DR: Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled.
Abstract: Caspases are a family of endoproteases that provide critical links in cell regulatory networks controlling inflammation and cell death. The activation of these enzymes is tightly controlled by their production as inactive zymogens that gain catalytic activity following signaling events promoting their aggregation into dimers or macromolecular complexes. Activation of apoptotic caspases results in inactivation or activation of substrates, and the generation of a cascade of signaling events permitting the controlled demolition of cellular components. Activation of inflammatory caspases results in the production of active proinflammatory cytokines and the promotion of innate immune responses to various internal and external insults. Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled.
2,127 citations