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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3001-3007. Prepublished online as a Blood First Edition Paper on August 7, 2009; DOI 10.1182/blood-2009-03-211334. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-03-211334v1 114/14/3001    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 Silva, F. P. G. Articles by Giphart-Gassler, M. PubMed PubMed Citation Articles by Silva, F. P. G. Articles by Giphart-Gassler, M. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Gene expression profiling of minimally differentiated acute myeloid leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status Fernando P. G. Silva1, Sigrid M. A. Swagemakers2,3, Claudia Erpelinck-Verschueren4, Bas J. Wouters4, Ruud Delwel4, Harry Vrieling1, Peter van der Spek2, Peter J. M. Valk4, and Micheline Giphart-Gassler1 1 Department of Toxicogenetics, Leiden University Medical Center, Leiden; and Departments of 2 Bioinformatics, 3 Cell Biology & Genetics, and 4 Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands Minimally differentiated acute myeloid leukemia (AML-M0) is defined by immature morphology and expression of early hematologic markers. By gene expression profiling (GEP) and subsequent unsupervised analysis of 35 AML-M0 samples and 253 previously reported AML cases, we demonstrate that AML-M0 cases express a unique signature that is largely separated from other molecular subtypes. Hematologic transcription regulators such as CEBPA, CEBPD, and ETV6, and the differentiation associated gene MPO appeared strongly down-regulated, in line with the primitive state of this leukemia. AML-M0 frequently carries loss-of-function RUNX1 mutation. Unsupervised analyses revealed a subdivision between AML-M0 cases with and without RUNX1 mutations. RUNX1 mutant AML-M0 samples showed a distinct up-regulation of B cell–related genes such as members of the B-cell receptor complex, transcription regulators RUNX3, ETS2, IRF8, or PRDM1, and major histocompatibility complex class II genes. Importantly, prediction with high accuracy of the AML-M0 subtype and prediction of patients carrying RUNX1 mutation within this subtype were possible based on the expression level of only a few transcripts. We propose that RUNX1 mutations in this AML subgroup cause lineage infidelity, leading to aberrant coexpression of myeloid and B-lymphoid genes. Furthermore, our results imply that AML-M0, although originally determined by morphology, constitutes a leukemia subgroup. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. P.G. Silva, I. Almeida, B. Morolli, G. Brouwer-Mandema, H. Wessels, R. Vossen, H. Vrieling, E. W.A. Marijt, P. J.M. Valk, H. C. Kluin-Nelemans, et al. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia Haematologica, November 1, 2009; 94(11): 1546 - 1554. [Abstract] [Full Text] [PDF]

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