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.
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.
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.
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)