Michelle M. Lebeau

Research Summary
Dr. Le Beau’s research focuses on the molecular analysis of the recurring chromosomal abnormalities in human leukemias and lymphomas, correlating specific abnormalities with morphological and clinical features and the development of risk-adapted therapy. Ongoing projects include the molecular cloning of haploinsufficient myeloid leukemia-related genes involved in the del(5q) characteristic of therapy-related acute myeloid leukemia; development and characterization of murine models recapitulating the genetic mutations in acute myeloid leukemia and identification of secondary, cooperating mutations and genetic pathways to leukemogenesis; and the application of murine models for pre-clinical drug testing.
Keywords
Molecular analysis of genetic pathways leading to myeloid leukemias, Preclinical studies using mouse models, Development of mouse models for human leukemias
Education
  • University of Illinois Medical Center, Chicago, IL, PhD Genetics 06/1981
  • University of Illinois Medical Center, Chicago, IL, MS Genetics 06/1978
Biosciences Graduate Program Association
Awards & Honors
  • 2011 - Arthur and Marian Edelstein Professor of Medicine University of Chicago
Publications
  1. McNerney ME, Godley LA, Le Beau MM. Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 2017 08 24; 17(9):513-527. View in: PubMed

  2. Stoddart A, Wang J, Hu C, Fernald AA, Davis EM, Cheng JX, Le Beau MM. Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model. Blood. 2017 06 01; 129(22):2959-2970. View in: PubMed

  3. 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. KRAS Allelic Imbalance Enhances Fitness and Modulates MAP Kinase Dependence in Cancer. Cell. 2017 02 23; 168(5):817-829.e15. View in: PubMed

  4. Yap KL, Furtado LV, Kiyotani K, Curran E, Stock W, McNeer JL, Kadri S, Segal JP, Nakamura Y, Le Beau MM, Gurbuxani S, Raca G. Diagnostic evaluation of RNA sequencing for the detection of genetic abnormalities associated with Ph-like acute lymphoblastic leukemia (ALL). Leuk Lymphoma. 2017 04; 58(4):950-958. View in: PubMed

  5. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D. Cytopenia levels for aiding establishment of the diagnosis of myelodysplastic syndromes. Blood. 2016 10 20; 128(16):2096-2097. View in: PubMed

  6. Jiang X, Bugno J, Hu C, Yang Y, Herold T, Qi J, Chen P, Gurbuxani S, Arnovitz S, Strong J, Ferchen K, Ulrich B, Weng H, Wang Y, Huang H, Li S, Neilly MB, Larson RA, Le Beau MM, Bohlander SK, Jin J, Li Z, Bradner JE, Hong S, Chen J. Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted miR-150 Nanoparticles. Cancer Res. 2016 08 01; 76(15):4470-80. View in: PubMed

  7. Jiang X, Hu C, Arnovitz S, Bugno J, Yu M, Zuo Z, Chen P, Huang H, Ulrich B, Gurbuxani S, Weng H, Strong J, Wang Y, Li Y, Salat J, Li S, Elkahloun AG, Yang Y, Neilly MB, Larson RA, Le Beau MM, Herold T, Bohlander SK, Liu PP, Zhang J, Li Z, He C, Jin J, Hong S, Chen J. miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia. Nat Commun. 2016 04 26; 7:11452. View in: PubMed

  8. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 05 19; 127(20):2391-405. View in: PubMed

  9. 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. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer Discov. 2016 05; 6(5):501-15. View in: PubMed

  10. 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. 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. Haematologica. 2016 06; 101(6):e232-6. View in: PubMed

  11. Vasanthakumar A, Arnovitz S, Marquez R, Lepore J, Rafidi G, Asom A, Weatherly M, Davis EM, Neistadt B, Duszynski R, Vardiman JW, Le Beau MM, Godley LA, Churpek JE. Brca1 deficiency causes bone marrow failure and spontaneous hematologic malignancies in mice. Blood. 2016 Jan 21; 127(3):310-3. View in: PubMed

  12. Churpek JE, Marquez R, Neistadt B, Claussen K, Lee MK, Churpek MM, Huo D, Weiner H, Bannerjee M, Godley LA, Le Beau MM, Pritchard CC, Walsh T, King MC, Olopade OI, Larson RA. Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia. Cancer. 2016 Jan 15; 122(2):304-11. View in: PubMed

  13. Sundaravel S, Duggan R, Bhagat T, Ebenezer DL, Liu H, Yu Y, Bartenstein M, Unnikrishnan M, Karmakar S, Liu TC, Torregroza I, Quenon T, Anastasi J, McGraw KL, Pellagatti A, Boultwood J, Yajnik V, Artz A, Le Beau MM, Steidl U, List AF, Evans T, Verma A, Wickrema A. Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes. Proc Natl Acad Sci U S A. 2015 Nov 17; 112(46):E6359-68. View in: PubMed

  14. Stoddart A, Nakitandwe J, Chen SC, Downing JR, Le Beau MM. Haploinsufficient loss of multiple 5q genes may fine-tune Wnt signaling in del(5q) therapy-related myeloid neoplasms. Blood. 2015 Dec 24; 126(26):2899-901. View in: PubMed

  15. Li Z, Chen P, Su R, Li Y, Hu C, Wang Y, Arnovitz S, He M, Gurbuxani S, Zuo Z, Elkahloun AG, Li S, Weng H, Huang H, Neilly MB, Wang S, Olson EN, Larson RA, Le Beau MM, Zhang J, Jiang X, Wei M, Jin J, Liu PP, Chen J. Overexpression and knockout of miR-126 both promote leukemogenesis. Blood. 2015 Oct 22; 126(17):2005-15. View in: PubMed

  16. 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. Dissecting the role of aberrant DNA methylation in human leukaemia. Nat Commun. 2015 May 22; 6:7091. View in: PubMed

  17. 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. Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis. Nat Genet. 2015 May; 47(5):539-43. View in: PubMed

  18. Wood AM, Rendtlew Danielsen JM, Lucas CA, Rice EL, Scalzo D, Shimi T, Goldman RD, Smith ED, Le Beau MM, Kosak ST. TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends. Nat Commun. 2014 Nov 17; 5:5467. View in: PubMed

  19. Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM, Reynaud D, Alvarez S, Diolaiti ME, Ugarte F, Forsberg EC, Le Beau MM, Stohr BA, Méndez J, Morrison CG, Passegué E. Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature. 2014 Aug 14; 512(7513):198-202. View in: PubMed

  20. McNerney ME, Brown CD, Peterson AL, Banerjee M, Larson RA, Anastasi J, Le Beau MM, White KP. The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q). Br J Haematol. 2014 Aug; 166(4):550-6. View in: PubMed

  21. Chen C, Liu Y, Rappaport AR, Kitzing T, Schultz N, Zhao Z, Shroff AS, Dickins RA, Vakoc CR, Bradner JE, Stock W, LeBeau MM, Shannon KM, Kogan S, Zuber J, Lowe SW. MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia. Cancer Cell. 2014 May 12; 25(5):652-65. View in: PubMed

  22. Stoddart A, Fernald AA, Wang J, Davis EM, Karrison T, Anastasi J, Le Beau MM. Haploinsufficiency of del(5q) genes, Egr1 and Apc, cooperate with Tp53 loss to induce acute myeloid leukemia in mice. Blood. 2014 Feb 13; 123(7):1069-78. View in: PubMed

  23. 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. ß-Catenin induces T-cell transformation by promoting genomic instability. Proc Natl Acad Sci U S A. 2014 Jan 07; 111(1):391-6. View in: PubMed

  24. Stoddart A, Wang J, Fernald AA, Karrison T, Anastasi J, Le Beau MM. Cell intrinsic and extrinsic factors synergize in mice with haploinsufficiency for Tp53, and two human del(5q) genes, Egr1 and Apc. Blood. 2014 Jan 09; 123(2):228-38. View in: PubMed

  25. Mrozek K, Arthur D, Karakousis C, Koduru P, Lebeau M, Pettenati M, Tantravahi R, Mrozek E, Perezmesa C, Rao U, Frankel S, Davey F, Bloomfield C. Der(16)T(1-16) is a nonrandom secondary chromosome aberration in many types of human neoplasia, including myxoid liposarcoma, rhabdomyosarcoma and Philadelphia-chromosome-positive acute lymphoblastic-leukemia. Int J Oncol. 1995 Mar; 6(3):531-8. View in: PubMed

  26. Lee S, Chen J, Zhou G, Shi RZ, Bouffard GG, Kocherginsky M, Ge X, Sun M, Jayathilaka N, Kim YC, Emmanuel N, Bohlander SK, Minden M, Kline J, Ozer O, Larson RA, LeBeau MM, Green ED, Trent J, Karrison T, Liu PP, Wang SM, Rowley JD. Gene expression profiles in acute myeloid leukemia with common translocations using SAGE. Proc Natl Acad Sci U S A. 2006 Jan 24; 103(4):1030-5. View in: PubMed

  27. Watson PA, Ellwood-Yen K, King JC, Wongvipat J, Lebeau MM, Sawyers CL. Context-dependent hormone-refractory progression revealed through characterization of a novel murine prostate cancer cell line. Cancer Res. 2005 Dec 15; 65(24):11565-71. View in: PubMed

  28. Le Beau MM, Davis EM, Patel B, Phan VT, Sohal J, Kogan SC. Recurring chromosomal abnormalities in leukemia in PML-RARA transgenic mice identify cooperating events and genetic pathways to acute promyelocytic leukemia. Blood. 2003 Aug 01; 102(3):1072-4. View in: PubMed

  29. Le Beau MM, Bitts S, Davis EM, Kogan SC. Recurring chromosomal abnormalities in leukemia in PML-RARA transgenic mice parallel human acute promyelocytic leukemia. Blood. 2002 Apr 15; 99(8):2985-91. View in: PubMed

  30. Qian Z, Lin C, Espinosa R, LeBeau M, Rosner MR. Cloning and characterization of MST4, a novel Ste20-like kinase. J Biol Chem. 2001 Jun 22; 276(25):22439-45. View in: PubMed

  31. Cho JH, Nicolae DL, Ramos R, Fields CT, Rabenau K, Corradino S, Brant SR, Espinosa R, LeBeau M, Hanauer SB, Bodzin J, Bonen DK. Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease. Hum Mol Genet. 2000 May 22; 9(9):1425-32. View in: PubMed

  32. Bernstein J, Dastugue N, Haas OA, Harbott J, Heerema NA, Huret JL, Landman-Parker J, LeBeau MM, Leonard C, Mann G, Pages MP, Perot C, Pirc-Danoewinata H, Roitzheim B, Rubin CM, Slociak M, Viguie F. Nineteen cases of the t(1;22)(p13;q13) acute megakaryblastic leukaemia of infants/children and a review of 39 cases: report from a t(1;22) study group. Leukemia. 2000 Jan; 14(1):216-8. View in: PubMed

  33. Camoretti-Mercado B, Forsythe SM, LeBeau MM, Espinosa R, Vieira JE, Halayko AJ, Willadsen S, Kurtz B, Ober C, Evans GA, Thweatt R, Shapiro S, Niu Q, Qin Y, Padrid PA, Solway J. Expression and cytogenetic localization of the human SM22 gene (TAGLN). Genomics. 1998 May 01; 49(3):452-7. View in: PubMed

  34. Chekmareva MA, Hollowell CM, Smith RC, Davis EM, LeBeau MM, Rinker-Schaeffer CW. Localization of prostate cancer metastasis-suppressor activity on human chromosome 17. Prostate. 1997 Dec 01; 33(4):271-80. View in: PubMed

  35. Larson RA, LeBeau MM, Vardiman JW, Rowley JD. Myeloid leukemia after hematotoxins. Environ Health Perspect. 1996 Dec; 104 Suppl 6:1303-7. View in: PubMed

  36. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15; 89(6):2079-88. View in: PubMed

  37. Hidai H, Quertermous EE, Espinosa R, LeBeau MM, Quertermous T. Genomic organization and chromosomal localization of the gene TCF15 encoding the early mesodermal basic helix-loop-helix factor bHLH-EC2. Genomics. 1995 Dec 10; 30(3):598-601. View in: PubMed

  38. Tanabe S, Zeleznik-Le NJ, Kobayashi H, Vignon C, Espinosa R, LeBeau MM, Thirman MJ, Rowley JD. Analysis of the t(6;11)(q27;q23) in leukemia shows a consistent breakpoint in AF6 in three patients and in the ML-2 cell line. Genes Chromosomes Cancer. 1996 Apr; 15(4):206-16. View in: PubMed

  39. Brown LJ, Stoffel M, Moran SM, Fernald AA, Lehn DA, LeBeau MM, MacDonald MJ. Structural organization and mapping of the human mitochondrial glycerol phosphate dehydrogenase-encoding gene and pseudogene. Gene. 1996 Jun 26; 172(2):309-12. View in: PubMed

  40. Wong DA, Davis EM, LeBeau M, Springer TA. Cloning and chromosomal localization of a novel gene-encoding a human beta 2-integrin alpha subunit. Gene. 1996 Jun 01; 171(2):291-4. View in: PubMed

  41. Lia KM, Bruns GA, LeBeau MM, Silverman GA. pMCT108.2 is a chimaeric clone which physically maps to human chromosome bands 9q33 (D9S203) and 18q21.1 (D18S24). Hum Mol Genet. 1993 Mar; 2(3):332. View in: PubMed

  42. Silverman GA, Jenkins R, Bruns GA, LeBeau MM. Reassignment of pEFD70.3 (D18S23) to human chromosome band 21q22.2 (D21S412) by physical mapping. Hum Mol Genet. 1993 Mar; 2(3):331. View in: PubMed

  43. Nucifora G, Birn DJ, Espinosa R, Erickson P, LeBeau MM, Roulston D, McKeithan TW, Drabkin H, Rowley JD. Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. Blood. 1993 May 15; 81(10):2728-34. View in: PubMed

  44. Nucifora G, Birn DJ, Erickson P, Gao J, LeBeau MM, Drabkin HA, Rowley JD. Detection of DNA rearrangements in the AML1 and ETO loci and of an AML1/ETO fusion mRNA in patients with t(8;21) acute myeloid leukemia. Blood. 1993 Feb 15; 81(4):883-8. View in: PubMed

  45. Zhang LQ, Downie PA, Goodell WR, McCabe NR, LeBeau MM, Morgan R, Sklar J, Raimondi SC, Miley D, Goldberg A, et al. Establishment of cell lines from B-cell precursor acute lymphoblastic leukemia. Leukemia. 1993 Nov; 7(11):1865-74. View in: PubMed

  46. Ozer H, George SL, Schiffer CA, Rao K, Rao PN, Wurster-Hill DH, Arthur DD, Powell B, Gottlieb A, Peterson BA, Rai K, Testa JR, LeBeau M, Tantravahi R, Bloomfield CD. Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583. Blood. 1993 Nov 15; 82(10):2975-84. View in: PubMed

  47. Hayani A, Suarez CR, Molnar Z, LeBeau M, Godwin J. Acute myeloid leukaemia in a patient with Seckel syndrome. J Med Genet. 1994 Feb; 31(2):148-9. View in: PubMed

  48. Varanasi U, Chu R, Chu S, Espinosa R, LeBeau MM, Reddy JK. Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization. Proc Natl Acad Sci U S A. 1994 Apr 12; 91(8):3107-11. View in: PubMed

  49. Marlton P, Claxton DF, Liu P, Estey EH, Beran M, LeBeau M, Testa JR, Collins FS, Rowley JD, Siciliano MJ. Molecular characterization of 16p deletions associated with inversion 16 defines the critical fusion for leukemogenesis. Blood. 1995 Feb 01; 85(3):772-9. View in: PubMed

  50. Ponnambalam S, Jackson AP, LeBeau MM, Pravtcheva D, Ruddle FH, Alibert C, Parham P. Chromosomal location and some structural features of human clathrin light-chain genes (CLTA and CLTB). Genomics. 1994 Dec; 24(3):440-4. View in: PubMed

  51. Burnett RC, Espinosa R, Shows TB, Eddy RL, LeBeau MM, Rowley JD, Diaz MO. Molecular analysis of a t(11;14)(q23;q11) from a patient with null-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer. 1993 May; 7(1):38-46. View in: PubMed

  52. Zhou J, Neidigh JL, Espinosa R, LeBeau MM, McClain DA. Human glutamine: fructose-6-phosphate amidotransferase: characterization of mRNA and chromosomal assignment to 2p13. Hum Genet. 1995 Jul; 96(1):99-101. View in: PubMed

  53. Lawrence HJ, Sauvageau G, Ahmadi N, Lopez AR, LeBeau MM, Link M, Humphries K, Largman C. Stage- and lineage-specific expression of the HOXA10 homeobox gene in normal and leukemic hematopoietic cells. Exp Hematol. 1995 Oct; 23(11):1160-6. View in: PubMed

  54. Vaxillaire M, Vionnet N, Vigouroux C, Sun F, Espinosa R, Lebeau MM, Stoffel M, Lehto M, Beckmann JS, Detheux M, et al. Search for a third susceptibility gene for maturity-onset diabetes of the young. Studies with eleven candidate genes. Diabetes. 1994 Mar; 43(3):389-95. View in: PubMed

  55. LeBeau MM, Rowley JD. Heritable fragile sites in cancer. Nature. 1984 Apr 12-18; 308(5960):607-8. View in: PubMed

  56. Staunton DE, Fisher RC, LeBeau MM, Lawrence JB, Barton DE, Francke U, Dustin M, Thorley-Lawson DA. Blast-1 possesses a glycosyl-phosphatidylinositol (GPI) membrane anchor, is related to LFA-3 and OX-45, and maps to chromosome 1q21-23. J Exp Med. 1989 Mar 01; 169(3):1087-99. View in: PubMed

  57. Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa R, Patel Y, Harden A, Rubinelli P, Smith SD, LeBeau MM, Rowley JD, et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. 1991 Dec 01; 88(23):10735-9. View in: PubMed

  58. Lowney P, Corral J, Detmer K, LeBeau MM, Deaven L, Lawrence HJ, Largman C. A human Hox 1 homeobox gene exhibits myeloid-specific expression of alternative transcripts in human hematopoietic cells. Nucleic Acids Res. 1991 Jun 25; 19(12):3443-9. View in: PubMed

  59. Ohagi S, LaMendola J, LeBeau MM, Espinosa R, Takeda J, Smeekens SP, Chan SJ, Steiner DF. Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues. Proc Natl Acad Sci U S A. 1992 Jun 01; 89(11):4977-81. View in: PubMed

  60. McKeithan TW, Warshawsky L, Espinosa R, LeBeau MM. Molecular cloning of the breakpoints of a complex Philadelphia chromosome translocation: identification of a repeated region on chromosome 17. Proc Natl Acad Sci U S A. 1992 Jun 01; 89(11):4923-7. View in: PubMed