MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia
- Shuangli Mi†,
- Jun Lu‡,§,
- Miao Sun†,
- Zejuan Li†,
- Hao Zhang‡,
- Mary Beth Neilly†,
- Yungui Wang¶,
- Zhijian Qian†,
- Jie Jin¶,
- Yanming Zhang†,
- Stefan K. Bohlander‖,
- Michelle M. Le Beau†,
- Richard A. Larson†,
- Todd R. Golub‡,§,††,‡‡,
- Janet D. Rowley†,‡‡, and
- Jianjun Chen†,‡‡
- †Department of Medicine, University of Chicago, Chicago, IL 60637;
- ‡Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02141;
- §Department of Pediatric Oncology, Dana–Farber Cancer Institute, Boston, MA 02115;
- ¶Institute of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, People's Republic of China;
- ‖Department of Medicine III, University of Munich Hospital Grosshadern and Clinical Cooperative Group “Leukemia,” GSF–National Research Center for Environment and Health, 81377 Munich, Germany; and
- ††Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115
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Contributed by Janet D. Rowley, October 8, 2007 (received for review August 30, 2007)
Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, whereas acute myeloid leukemia (AML) is the most common acute leukemia in adults. In general, ALL has a better prognosis than AML. To understand the distinct mechanisms in leukemogenesis between ALL and AML and to identify markers for diagnosis and treatment, we performed a large-scale genome-wide microRNA (miRNA, miR) expression profiling assay and identified 27 miRNAs that are differentially expressed between ALL and AML. Among them, miR-128a and -128b are significantly overexpressed, whereas let-7b and miR-223 are significantly down-regulated in ALL compared with AML. They are the most discriminatory miRNAs between ALL and AML. Using the expression signatures of a minimum of two of these miRNAs resulted in an accuracy rate of >95% in the diagnosis of ALL and AML. The differential expression patterns of these four miRNAs were validated further through large-scale real-time PCR on 98 acute leukemia samples covering most of the common cytogenetic subtypes, along with 10 normal control samples. Furthermore, we found that overexpression of miR-128 in ALL was at least partly associated with promoter hypomethylation and not with an amplification of its genomic locus. Taken together, we showed that expression signatures of as few as two miRNAs could accurately discriminate ALL from AML, and that epigenetic regulation might play an important role in the regulation of expression of miRNAs in acute leukemias.
Footnotes
- ‡‡To whom correspondence may be addressed. E-mail: golub{at}broad.mit.edu, jrowley{at}medicine.bsd.uchicago.edu, or jchen{at}medicine.bsd.uchicago.edu
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Author contributions: S.M., J.L., M.S., and Z.L. contributed equally to this work; J.D.R. and J.C. designed research; S.M., J.L., M.S., Z.L., H.Z., M.B.N., and Y.W. performed research; J.L., Z.Q., J.J., Y.Z., S.K.B., M.M.L.B., R.A.L., and T.R.G. contributed new reagents/analytic tools; S.M., J.L., M.S., Z.L., and J.C. analyzed data; and J.D.R. and J.C. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0709313104/DC1.
- © 2007 by The National Academy of Sciences of the USA
