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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3158-3166. Prepublished online as a Blood First Edition Paper on July 27, 2009; DOI 10.1182/blood-2009-02-202465. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-02-202465v1 114/15/3158    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Gentles, A. J. Articles by Plevritis, S. K. PubMed PubMed Citation Articles by Gentles, A. J. Articles by Plevritis, S. K. Related Collections Free Research Articles Lymphoid Neoplasia Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS A pluripotency signature predicts histologic transformation and influences survival in follicular lymphoma patients Andrew J. Gentles1,*, Ash A. Alizadeh2,3,*, Su-In Lee4, June H. Myklebust3, Catherine M. Shachaf5, Babak Shahbaba6, Ronald Levy2,3, Daphne Koller4, and Sylvia K. Plevritis1 1 Department of Radiology, Divisions of 2 Hematology and 3 Oncology, Department of Medicine, and Departments of 4 Computer Science and 5 Microbiology and Immunology, Stanford University School of Medicine, CA; and 6 Department of Statistics, University of California, Irvine Histologic transformation (HT) of follicular lymphoma to diffuse large B-cell lymphoma (DLBCL-t) is associated with accelerated disease course and drastically worse outcome, yet the underlying mechanisms are poorly understood. We show that a network of gene transcriptional modules underlies HT. Central to the network hierarchy is a signature strikingly enriched for pluripotency-related genes. These genes are typically expressed in embryonic stem cells (ESCs), including MYC and its direct targets. This core ESC-like program was independent of proliferation/cell-cycle and overlapped but was distinct from normal B-cell transcriptional programs. Furthermore, we show that the ESC program is correlated with transcriptional programs maintaining tumor phenotype in transgenic MYC-driven mouse models of lymphoma. Although our approach was to identify HT mechanisms rather than to derive an optimal survival predictor, a model based on ESC/differentiation programs stratified patient outcomes in 2 independent patient cohorts and was predictive of propensity of follicular lymphoma tumors to transform. Transformation was associated with an expression signature combining high expression of ESC transcriptional programs with reduced expression of stromal programs. Together, these findings suggest a central role for an ESC-like signature in the mechanism of HT and provide new clues for potential therapeutic targets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Stem cell mimicry: key to transformation? Emanuela Carlotti and John G. Gribben Blood 2009 114: 3133-3134. [Abstract] [Full Text] [PDF] This article has been cited by other articles: E. Carlotti and J. G. Gribben Stem cell mimicry: key to transformation? Blood, October 8, 2009; 114(15): 3133 - 3134. [Abstract] [Full Text] [PDF]

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