Michelle Le Beau, Ph.D.

Professor

Research Description

Human tumors are characterized by recurring chromosomal abnormalities. During the past few years, the genes that are located at the breakpoints of a number of recurring chromosomal abnormalities in human tumors have been identified. Molecular analysis has revealed that alterations in the level of expression of these genes, or in the properties of the encoded proteins resulting from the chromosomal rearrangement, play an integral role in the process of malignant transformation. My research interests are:

  • to identify the recurring chromosomal abnormalities in human tumors;
  • to correlate specific chromosomal abnormalities with morphological and clinical features of the neoplastic disease, such as response to therapy and survival;
  • to identify the genes located at the breakpoints of the recurring abnormalities using the techniques of molecular genetics, and to examine their function in malignant cells characterized by these chromosomal abnormalities;
  • to localize genes to human chromosomes by using the technique of in situ chromosomal hybridization and to examine the location of specific genes relative to the breakpoints of recurring abnormalities in hematopoietic neoplastic diseases; and
  • to examine the relationship of chromosomal fragile sites (loci which are prone to undergo breakage and rearrangement) and cancer-specific breakpoints.

Selected Publications

Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model.
Stoddart A, Wang J, Hu C, Fernald AA, Davis EM, Cheng JX, Le Beau MM
(2017 Mar) Blood. 2017 Mar 27. pii: blood-2016-08-736454. doi: 10.1182/blood-2016-08-736454. 28348148

KRAS Allelic Imbalance Enhances Fitness and Modulates MAP Kinase Dependence in Cancer.
Burgess MR, Hwang E, Mroue R, Bielski CM, Wandler AM, Huang BJ, Firestone AJ, Young A, Lacap JA, Crocker L, Asthana S, Davis EM, Xu J, Akagi K, Le Beau MM, Li Q, Haley B, Stokoe D, Sampath D, Taylor BS, Evangelista M, Shannon K
(2017 Feb) Cell. 2017 Feb 23;168(5):817-829.e15. doi: 10.1016/j.cell.2017.01.020. Epub 2017 Feb 16. 28215705

Retroviral insertional mutagenesis identifies the del(5q) genes, CXXC5, TIFAB and ETF1, as well as the Wnt pathway, as potential targets in del(5q) myeloid neoplasms.
Stoddart A, Qian Z, Fernald AA, Bergerson RJ, Wang J, Karrison T, Anastasi J, Bartom ET, Sarver AL, McNerney ME, Largaespada DA, Le Beau MM
(2016 Jun) Haematologica. 2016 Jun;101(6):e232-6. doi: 10.3324/haematol.2015.139527. Epub 2016 Mar 4. 26944478 (Full Text)

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW
(2016 May) Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11. 27069254

DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia.
Meyer SE, Qin T, Muench DE, Masuda K, Venkatasubramanian M, Orr E, Suarez L, Gore SD, Delwel R, Paietta E, Tallman MS, Fernandez H, Melnick A, Le Beau MM, Kogan S, Salomonis N, Figueroa ME, Grimes HL
(2016 May) Cancer Discov. 2016 May;6(5):501-15. doi: 10.1158/2159-8290.CD-16-0008. Epub 2016 Mar 25. 27016502 (Full Text)

Haploinsufficient loss of multiple 5q genes may fine-tune Wnt signaling in del(5q) therapy-related myeloid neoplasms.
Stoddart A, Nakitandwe J, Chen SC, Downing JR, Le Beau MM
(2015 Dec) Blood. 2015 Dec 24;126(26):2899-901. doi: 10.1182/blood-2015-10-673228. Epub 2015 Nov 13. 26567158 (Full Text)

Knockdown of Hnrnpa0, a del(5q) gene, alters myeloid cell fate in murine cells through regulation of AU-rich transcripts.
Young DJ, Stoddart A, Nakitandwe J, Chen SC, Qian Z, Downing JR, Le Beau MM
(2014 Jun) Haematologica. 2014 Jun;99(6):1032-40. doi: 10.3324/haematol.2013.098657. Epub 2014 Feb 14. 24532040 (Full Text)

Haploinsufficiency of del(5q) genes, Egr1 and Apc, cooperate with Tp53 loss to induce acute myeloid leukemia in mice.
Stoddart A, Fernald AA, Wang J, Davis EM, Karrison T, Anastasi J, Le Beau MM
(2014 Feb) Blood. 2014 Feb 13;123(7):1069-78. doi: 10.1182/blood-2013-07-517953. Epub 2013 Dec 31. 24381225 (Full Text)

Cell intrinsic and extrinsic factors synergize in mice with haploinsufficiency for Tp53, and two human del(5q) genes, Egr1 and Apc.
Stoddart A, Wang J, Fernald AA, Karrison T, Anastasi J, Le Beau MM
(2014 Jan) Blood. 2014 Jan 9;123(2):228-38. doi: 10.1182/blood-2013-05-506568. Epub 2013 Nov 21. 24264229 (Full Text)

beta-Catenin induces T-cell transformation by promoting genomic instability.
Dose M, Emmanuel AO, Chaumeil J, Zhang J, Sun T, Germar K, Aghajani K, Davis EM, Keerthivasan S, Bredemeyer AL, Sleckman BP, Rosen ST, Skok JA, Le Beau MM, Georgopoulos K, Gounari F
(2014 Jan) Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):391-6. doi: 10.1073/pnas.1315752111. Epub 2013 Dec 26. 24371308 (Full Text)

Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation.
Xu J, Haigis KM, Firestone AJ, McNerney ME, Li Q, Davis E, Chen SC, Nakitandwe J, Downing J, Jacks T, Le Beau MM, Shannon K
(2013 Sep) Cancer Discov. 2013 Sep;3(9):993-1001. doi: 10.1158/2159-8290.CD-13-0096. Epub 2013 Jun 3. 23733505 (Full Text)

Revised international prognostic scoring system for myelodysplastic syndromes.
Greenberg PL et al.
(2012 Sep) Blood. 2012 Sep 20;120(12):2454-65. Epub 2012 Jun 27. 22740453 (Full Text)

Activation of Wnt/beta-catenin protein signaling induces mitochondria-mediated apoptosis in hematopoietic progenitor cells.
Ming M, Wang S, Wu W, Senyuk V, Le Beau MM, Nucifora G, Qian Z
(2012 Jun) J Biol Chem. 2012 Jun 29;287(27):22683-90. doi: 10.1074/jbc.M112.342089. Epub 2012 May 15. 22589536 (Full Text)

New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.
Schanz J, Tuchler H, Sole F, Mallo M, Luno E, Cervera J, Granada I, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstocker M, Nosslinger T, Valent P, Giagounidis A, Aul C, Lubbert M, Stauder R, Krieger O, Garcia-Manero G, Faderl S, Pierce S, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D
(2012 Mar) J Clin Oncol. 2012 Mar 10;30(8):820-9. doi: 10.1200/JCO.2011.35.6394. Epub 2012 Feb 13. 22331955 (Full Text)

Haploinsufficiency of Apc leads to ineffective hematopoiesis.
Wang J, Fernald AA, Anastasi J, Le Beau MM, Qian Z
(2010 Apr) Blood. 2010 Apr 29;115(17):3481-8. doi: 10.1182/blood-2009-11-251835. Epub 2010 Jan 11. 20065296 (Full Text)

Impaired replication dynamics at the FRA3B common fragile site.
Palakodeti A, Lucas I, Jiang Y, Young DJ, Fernald AA, Karrison T, Le Beau MM
(2010 Jan) Hum Mol Genet. 2010 Jan 1;19(1):99-110. doi: 10.1093/hmg/ddp470. 19815620 (Full Text)

Common fragile sites are characterized by histone hypoacetylation.
Jiang Y, Lucas I, Young DJ, Davis EM, Karrison T, Rest JS, Le Beau MM
(2009 Dec) Hum Mol Genet. 2009 Dec 1;18(23):4501-12. doi: 10.1093/hmg/ddp410. Epub 2009 Aug 28. 19717471 (Full Text)

A critical role for Apc in hematopoietic stem and progenitor cell survival.
Qian Z, Chen L, Fernald AA, Williams BO, Le Beau MM
(2008 Sep) J Exp Med. 2008 Sep 1;205(9):2163-75. doi: 10.1084/jem.20080578. Epub 2008 Aug 25. 18725524 (Full Text)

Cancer: hay in a haystack.
Shannon KM, Le Beau MM
(2008 Jan) Nature. 2008 Jan 17;451(7176):252-3. doi: 10.1038/451252a. 18202630

High-throughput mapping of origins of replication in human cells.
Lucas I, Palakodeti A, Jiang Y, Young DJ, Jiang N, Fernald AA, Le Beau MM
(2007 Aug) EMBO Rep. 2007 Aug;8(8):770-7. Epub 2007 Jul 13. 17668008 (Full Text)

Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders.
Joslin JM, Fernald AA, Tennant TR, Davis EM, Kogan SC, Anastasi J, Crispino JD, Le Beau MM
(2007 Jul) Blood. 2007 Jul 15;110(2):719-26. Epub 2007 Apr 9. 17420284 (Full Text)

Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series.
Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, Vardiman JW, Rowley JD, Larson RA
(2003 Jul) Blood. 2003 Jul 1;102(1):43-52. Epub 2003 Mar 6. 12623843