Research Summary

My laboratory studies the cytogenetic changes, particularly chromosome translocations that occur in cells from patients with leukemia. We have been very active in cloning balanced translocations from various patients with leukemia, including those who previously had cancer treated with drugs that inhibit the function of DNA topoisomerase II.

We used the SAGE (serial analysis of gene expression) technique to improve strategies for identifying transcripts that are expressed at low levels. We found that about 50% of transcripts were novel, i.e. not represented in current databases. These transcripts may represent novel genes or alternatively spliced genes, or more likely, they may represent non-coding RNAs which may regulate gene transcription. We have developed a custom microarray to diagnose the common translocations in human AML; in addition we are analyzing the expression pattern of micro RNAs in different leukemias. We have found that 2 miRs are sufficient to distinguish acute lymphoblastic leukemic from acute myeloblastic leukemia (AML). Moreover, within AML with common translocations, 3-7 miRs are sufficient to distinguish different translocations. We are currently analyzing the mechanism for alterations of miR expression; in one case, we have evidence that it may be increased or decreased methylation. We are also trying to identify the target genes of each miR because they might provide new insights for treating patients with leukemia.

Selected Publications

Zhang, Y., Strissel, P., Strick, R., Chen, J., Nucifora, G., LeBeau, M.M., Larson, R.A., Rowley, JD. Genomic DNA Breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia. Proc Natl Acad Sci USA 99:3070-5, 2002. (PubMed)

Rowley, J.D. The critical role of chromosome translocations in human leukemias. In: Annual Reviews of Genetics 32:495-519, 1998. (PubMed)

Rowley, JD. Chromosome translocations: dangerous liaisons revisited. Nature Reviews Cancer 1:245-250, 2001. (PubMed)

Chen, J., Sun, M., Kent, W.J., Huang, S., Xie, H., Wang, W., Zhou, Z., Zhang Shi, R., Rowley, J.D. Over 20% of human transcripts might form sense-antisense pairs. Nucleic Acids Research, 32(16): 4812-20, 2004. (PubMed)

Zou, G., Chen, J., Yoder, M., Wu, W., Rowley, J.D. Knockdown of Pu.1 by siRNA in CD34+ EB cells derived from mouse embryonic stem cells turn cell fate determination to pro-B cells. Proc Natl Acad Sci U S A, 102(37): 13236-41, 2005. (PubMed)

Lee, S., Chen, J., Zhou, G., Shi, R., Bouffard, G., Kocherginsky, M., Ge, X., Sun, M., Jayathilaka, N., Kim, Y., Emmanuel, N., Bohlander, S., Minden, M., Kline, J., Ozer, O., Larson, R., LeBeau, M., Green, E., Trent, J., Karrison, T., Liu, P., Wang, S.M., Rowley, J.D. Gene Expression Profiles in Acute Myeloid Leukemia with Common Translocations using SAGE. Proc Natl Acad Sci U S A, 103(4): 1030-5, 2006. (PubMed)

Zhang, Y., Rowley, J.D. Chromatin structural elements and chromosomal translocations in leukemia. DNA Repair, 5(9-10): 1282-97, 2006. (PubMed)

Mi, S., Lu, J., Sun, M., Li, Z., Zhang, H., Neilly, M.B., Wang, Y., Qian, Z., Jin, J., Zhang, Y., Bohlander, S.K., Le Beau, M.M., Larson, R.A., Golub, T.R., Rowley, J.D., Chen, J. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 2007 Dec 4 [Epub ahead of print] (PubMed)