Janet Rowley, M.D.

Chromosome Rearrangements in Human Malignant Cells (Leukemias and Lymphomas)

Research Summary

Members of the laboratory continue to map and clone translocation breakpoints. However we also focus on analyzing the potential mechanisms leading to translocations, by cloning the genomic sequences at breakpoints, mapping topoisomerase II cleavage sites and nucleosome phasing. A major emphasis at present is the analysis of gene expression in normal human and murine hematopoietic cells as well as in various human leukemias. We use the SAGE (serial analysis of gene expression) technique to identify all of the transcripts present in these cells; thus we are not limited to known genes or ESTs and the data are quantitative. We have identified many novel transcripts in both normal and leukemic cells; the challenge is to determine the identity of these transcripts. We are using the SAGE data to construct a microarray dedicated to the accurate detection of common tranlocations in hunan acute myeloid leukemia.

Selected Papers

Odero MD, Carlson K, Lahortiga I, Calasanz MJ, Rowley JD. (2003). Molecular cytogenetic characterization of breakpoints in 19 patients with hematologic malignancies and 12p unbalanced translocations. Cancer Genet Cytogenet. 142(2):115-9.

Klein F, Feldhahn N, Lee S, Wang H, Ciuffi F, von Elstermann M, Toribio ML, Sauer H, Wartenberg M, Barath VS, Kronke M, Wernet P, Rowley JD, Muschen M.  (2003). T lymphoid differentiation in human bone marrow. Proc Natl Acad Sci U S A. 100(11):6747-52. Epub 2003 May 08.

Echlin-Bell DR, Smith LL, Li L, Strissel PL, Strick R, Gupta V, Banerjee J, Larson R, Relling MV, Raimondi SC, Hayashi Y, Taki T, Zeleznik-Le N, Rowley JD. (2003). Polymorphisms in the MLL breakpoint cluster region (BCR). Hum Genet. 113(1):80-91. Epub 2003 Mar 29.

Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, Vardiman JW, Rowley JD, Larson RA. (2003). Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood. 102(1):43-52. Epub 2003 Mar 06.

Zou GM, Wu W, Chen J, Rowley JD.  (2003). Duplexes of 21-nucleotide RNAs mediate RNA interference in differentiated mouse ES cells.Biol Cell. 95(6):365-71.PMID: 14519553

Zhang Y, Emmanuel N, Kamboj G, Chen J, Shurafa M, Van Dyke DL, Wiktor A, Rowley JD. (2004). PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22).
Genes Chromosomes Cancer. 40(4):365-70. PMID: 15188461

Helbling D, Mueller BU, Timchenko NA, Hagemeijer A, Jotterand M, Meyer-Monard S, Lister A, Rowley JD, Huegli B, Fey MF, Pabst T. (2004). The leukemic fusion gene AML1-MDS1-EVI1 suppresses CEBPA in acute myeloid leukemia by activation of Calreticulin. Proc Natl Acad Sci U S A. 101(36):13312-7. Epub 2004 Aug 23.

Chen J, Sun M, Kent WJ, Huang X, Xie H, Wang W, Zhou G, Shi RZ, Rowley JD. (2004). Over 20% of human transcripts might form sense-antisense pairs. Nucleic Acids Res. 32(16):4812-20. Print 2004.

Zhang Y, Zeleznik-Le N, Emmanuel N, Jayathilaka N, Chen J, Strissel P, Strick R, Li L, Neilly MB, Taki T, Hayashi Y, Kaneko Y, Schlegelberger B, Rowley JD. (2004). Characterization of genomic breakpoints in MLL and CBP in leukemia patients with t(11;16).Genes Chromosomes Cancer. 41(3):257-65.

Kobzev YN, Martinez-Climent J, Lee S, Chen J, Rowley JD. (2004). Analysis of translocations that involve the NUP98 gene in patients with 11p15 chromosomal rearrangements. Genes Chromosomes Cancer. 41(4):339-52.