- Arthur and Marian Edelstein Professor, Department of Medicine - Section of Hematology/Oncology, Department of Human Genetics, Ben May Department for Cancer Research, Committee on Cancer Biology, Committee on Genetics
- Director, The University of Chicago Comprehensive Cancer Center (UCCCC)
- Director, Cancer Cytogenetics Laboratory
Ph.D., University of Illinois-Chicago, 1981
M.S., University of Illinois-Chicago, 1978
B.S., Purdue University, 1976
The University of Chicago
AMB H212Q, (MC 1140)
5841 South Maryland Avenue
Chicago, Illinois 60637
Phone: (773) 702-0795
Website (Cancer Research Center)
Website (Ben May)
Molecular Analysis of Recurring Chromosomal Abnormalities in Human Tumors; Identification of Cooperating Mutations and Genetic Pathways Leading to Transformation
Human tumors are characterized by recurring chromosomal abnormalities as well as molecular changes that lead to the activation of oncogenes, and loss of function of tumor suppressor genes. Dr. Le Beau has been recognized for her work in identifying recurring cytogenetic abnormalities, in defining the clinical, morphological, and cytogenetic subsets of leukemia, in identifying the genetic pathways that lead to myeloid leukemias, and on the application of fluorescence in situ hybridization technology for clinical diagnostics and gene mapping.
Much of her work has focused on characterizing the cytogenetic, clinical, and morphologic features of therapy-related myeloid neoplasms (t-MN), an aggressive form of myelodysplastic syndrome or acute myeloid leukemia arising in patients who have been treated with cytotoxic therapy for a primary malignant disease, such as a solid tumor. The contributions of the Le Beau laboratory include: 1) the recognition that abnormalities of chromosomes 5 and/or 7 are the hallmark of t-MN following alkylating agent therapy; 2) delineation of a 970 kb commonly deleted segment (CDS) of 5q, and preparation of a genomic contig and transcript map of this region; 3) determining that the myeloid leukemia gene acts by haploinsufficiency and proposing that t-MN associated with a del(5q) results from the simultaneous loss of multiple haploinsufficient genes on 5q; 4) identifying the first haploinsufficient myeloid leukemia suppressor gene within the CDS of 5q, EGR1; 5) determining that APC (5q22.2) is haploinsufficient in myeloid neoplasms with a del(5q), that Apc is essential for the maintenance and survival of hematopoietic stem and progenitor cells in mice, and that haploinsufficiency results in a fatal macrocytic anemia, recapitulating characteristic features of t-MN with a del(5q); 6) demonstrating that haploinsufficiency of Egr1 and Apc cooperate to accelerate anemia onset; and 7) determining that loss of Tp53 in BM cells haploinsufficient for both Egr1 and Apc is permissive for the development of AML in mice, thereby establishing the first mouse model for t-MN with a del(5q). Ongoing projects include the delineation of additional genes on chromosome 5 that cooperate with EGR1 and APC in the pathogenesis of t-MN, as well as the analysis of the synergistic cross-talk between the bone marrow microenvironment or “stem cell niche” and hematopoietic stem cells during normal blood cell development and in leukemogenesis.
Amabile G, Di Ruscio A, Müller F, Welner RS, Yang H, Ebralidze AK, Zhang H, Levantini E, Qi L, Martinelli G, Brummelkamp T, Le Beau MM, Figueroa ME, Bock C, Tenen DG. (2015). "Dissecting the role of aberrant DNA methylation in human leukemia." Nat Commun. 6:7091.
Zhao Z, Chen CC, Rillahan CD, Shen R, Kitzing T, McNerney ME, Diaz-Flores E, Zuber J, Shannon K, Le Beau MM, Spector MS, Kogan SC, Lowe SW. (2015). "Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis." Nat Genet. 47(5):539-43.
Della Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres MA, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D, Greenberg PL, Cazzola M. (2015). "Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM)." Leukemia. [Epub ahead of print]
Wood AM, Rendtlew Danielsen JM, Lucas CA, Rice EL, Scalzo D, Shimi T, Goldman RD, Smith ED, Le Beau MM, Kosak ST. (2014). "TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends." Nat Commun. 5:5467.
Braulke F, Platzbecker U, Müller-Thomas C, Götze K, Germing U, Brümmendorf TH, Nolte F, Hofmann WK, Giagounidis AA, Lübbert M, Greenberg PL, Bennett JM, Solé F, Mallo M, Slovak ML, Ohyashiki K, Le Beau MM, Tüchler H, Pfeilstöcker M, Nösslinger T, Hildebrandt B, Shirneshan K, Aul C, Stauder R, Sperr WR, Valent P, Fonatsch C, Trümper L, Haase D, Schanz J. (2015). "Validation of cytogenetic risk groups according to INternational Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group." Haematologica. 100(2):205-13.