BACKGROUND: Metabolic dysregulation has been identified as an "emerging hallmark" of cancer. The heterotrimeric AMP-activated protein kinase (AMPK) complex is a central regulator of the metabolic system and an important component of the mTOR pathway and the p53 axis, making it uniquely positioned to influence carcinogenesis through its canonical functions in the metabolic arena, as well as through more traditional mechanisms such as regulation of apoptosis and angiogenesis. METHODS: We conducted a population-based genetic association study to examine the impact of mutations in AMPK subunit genes on risk of non-Hodgkin lymphoma (NHL). We also analyzed public microarray data to determine the expression of AMPK in NHL cells and to assess the influence of AMPK expression on overall survival in patients with NHL. RESULTS: We identified an AMPK subunit haplotype, which was significantly associated with NHL [OR, 5.44, 95% confidence interval (CI), 2.15-13.75] in women with no family history of cancer. Haplotypes in two subunits, PRKAA2 and PRKAG3, were nominally associated with the follicular and diffuse large B-cell lymphoma histologic subtypes, respectively, although these associations did not retain statistical significance after correction for multiple comparisons. Further, both of these subunits were differentially expressed (P < 0.05) in one or more lymphoma cell type, and higher expression of two versions of the AMPK-β subunit was significantly associated with increased 5-year survival among patients with NHL (P = 0.001 and P = 0.021). CONCLUSION: These results provide evidence for AMPK involvement in the pathogenesis and progression of NHL. IMPACT: These findings may lead to a novel area of research into NHL treatment and chemoprevention.
BACKGROUND: Metabolic dysregulation has been identified as an "emerging hallmark" of cancer. The heterotrimeric AMP-activated protein kinase (AMPK) complex is a central regulator of the metabolic system and an important component of the mTOR pathway and the p53 axis, making it uniquely positioned to influence carcinogenesis through its canonical functions in the metabolic arena, as well as through more traditional mechanisms such as regulation of apoptosis and angiogenesis. METHODS: We conducted a population-based genetic association study to examine the impact of mutations in AMPK subunit genes on risk of non-Hodgkin lymphoma (NHL). We also analyzed public microarray data to determine the expression of AMPK in NHL cells and to assess the influence of AMPK expression on overall survival in patients with NHL. RESULTS: We identified an AMPK subunit haplotype, which was significantly associated with NHL [OR, 5.44, 95% confidence interval (CI), 2.15-13.75] in women with no family history of cancer. Haplotypes in two subunits, PRKAA2 and PRKAG3, were nominally associated with the follicular and diffuse large B-cell lymphoma histologic subtypes, respectively, although these associations did not retain statistical significance after correction for multiple comparisons. Further, both of these subunits were differentially expressed (P < 0.05) in one or more lymphoma cell type, and higher expression of two versions of the AMPK-β subunit was significantly associated with increased 5-year survival among patients with NHL (P = 0.001 and P = 0.021). CONCLUSION: These results provide evidence for AMPK involvement in the pathogenesis and progression of NHL. IMPACT: These findings may lead to a novel area of research into NHL treatment and chemoprevention.
Authors: Yu Xuan Koo; Daniel S W Tan; Iain B H Tan; David W M Tai; Tam Ha; Whee Sze Ong; Richard Quek; Miriam Tao; Soon Thye Lim Journal: Leuk Lymphoma Date: 2011-06-10
Authors: Russell G Jones; David R Plas; Sara Kubek; Monica Buzzai; James Mu; Yang Xu; Morris J Birnbaum; Craig B Thompson Journal: Mol Cell Date: 2005-04-29 Impact factor: 17.970
Authors: M van Slegtenhorst; R de Hoogt; C Hermans; M Nellist; B Janssen; S Verhoef; D Lindhout; A van den Ouweland; D Halley; J Young; M Burley; S Jeremiah; K Woodward; J Nahmias; M Fox; R Ekong; J Osborne; J Wolfe; S Povey; R G Snell; J P Cheadle; A C Jones; M Tachataki; D Ravine; J R Sampson; M P Reeve; P Richardson; F Wilmer; C Munro; T L Hawkins; T Sepp; J B Ali; S Ward; A J Green; J R Yates; J Kwiatkowska; E P Henske; M P Short; J H Haines; S Jozwiak; D J Kwiatkowski Journal: Science Date: 1997-08-08 Impact factor: 47.728
Authors: Ulrich Jäger; Michael Fridrik; Markus Zeitlinger; Daniel Heintel; Georg Hopfinger; Sonja Burgstaller; Christine Mannhalter; Wilhelm Oberaigner; Edit Porpaczy; Cathrin Skrabs; Christine Einberger; Johannes Drach; Markus Raderer; Alexander Gaiger; Monique Putman; Richard Greil Journal: Haematologica Date: 2012-04-17 Impact factor: 9.941
Authors: Daniele Campa; Rainer Claus; Lucie Dostal; Angelika Stein; Jenny Chang-Claude; Karina Meidtner; Heiner Boeing; Anja Olsen; Anne Tjønneland; Kim Overvad; Laudina Rodríguez; Catalina Bonet; Maria-José Sánchez; Pilar Amiano; José María Huerta; Aurelio Barricarte; Kay-Tee Khaw; Nicholas Wareham; Ruth C Travis; Naomi E Allen; Antonia Trichopoulou; Christina Bamia; Vassiliki Benetou; Domenico Palli; Claudia Agnoli; Salvatore Panico; Rosario Tumino; Carlotta Sacerdote; Henk van Kranen; H Bas Bueno-de-Mesquita; Petra H M Peeters; Carla H van Gils; Per Lenner; Malin Sund; Eiliv Lund; Inger Torhild Gram; Sabina Rinaldi; Veronique Chajes; Isabelle Romieu; Pierre Engel; Marie Christine Boutron-Ruault; Françoise Clavel-Chapelon; Afshan Siddiq; Elio Riboli; Federico Canzian; Rudolf Kaaks Journal: Breast Cancer Res Treat Date: 2010-11-30 Impact factor: 4.872
Authors: Vanessa P Houde; Sara Donzelli; Andrea Sacconi; Sandra Galic; Joanne A Hammill; Jonathan L Bramson; Robert A Foster; Theodoros Tsakiridis; Bruce E Kemp; Giuseppe Grasso; Giovanni Blandino; Paola Muti; Gregory R Steinberg Journal: Mol Oncol Date: 2017-06-28 Impact factor: 6.603
Authors: Yuejiao Huang; Chunlei Peng; Jie Tang; Shitao Wang; Fan Yang; Qiufei Wang; Li Zhou; Lei Yang; Shaoqing Ju Journal: Ann Transl Med Date: 2021-09