Publications

Publications

 

Featured Publications


The Armstrong lab uses genomic approaches to characterize childhood acute lymphoblastic leukemias (ALL) with a goal of developing a better understanding of leukemogenesis and developing new therapeutic approaches. These studies have had a direct impact on our understanding of the biology of ALL and therapeutic intervention:

MLL translocations specify a distinct gene expression profile, distinguishing a unique leukemia.
Armstrong, S.A., Staunton, J.E., Silverman, L.B., Pieters, R., den Boer, M.L., Minden, M.D., Sallan, S.E., Lander, E.S., Golub, T.R. Korsmeyer, S.J.
Nature Genetics. 2002 Jan;30(1):41-7. PMID: 11731795.

Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance.
Wei, G., Twomey, D., Lamb, J., Agarwal, J., Stam, R., Opferman, J. T., Sallan, S.E., den Boer, M.L., Pieters, R., Golub, T.R., Armstrong, S.A.
Cancer Cell. 2006 Oct;10(4):331-42. PMID: 17010674.

The Connectivity Map: using gene-expression signatures to connect small molecules, genes and disease.
Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, Reich M, Hieronymus H, Wei G, Armstrong SA, Haggarty SJ, Clemons PA, Wei R, Carr SA, Lander ES, Golub TR.
Science. 2006: Sep 29;313(5795):1929-35. PMID: 17008526.

Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia.
Mar B, Bullinger L, McClean K, Grauman P, Harris M, Stevenson K, Neuberg D, Sinha A, Sallan S, Silverman L, Kung A, Nigro L, Ebert B, Armstrong SA.
Nature Communications. 2014 Mar 24; 5:3469. PMID: 24662245.


The lab is also interested in the mechanisms that control leukemic self-renewal and how selfrenewal of cancer cells is related to normal stem cell biology. We have used genome-scale approaches to characterize the role of specific genes in mouse hematopoietic cells and mouse models of leukemia. These studies have helped define the identity of cancer stem cells and mechanisms of self-renewal in leukemia:

Transformation from committed progenitor to leukaemia stem cell initiated by MLL AF-9.
Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA.
Nature. 2006 Aug 17;442(7104):818-22. PMID: 16862118.

The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML.
Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA.
Science. 2010 Mar 26;327(5973):1650-3. PMID: 20339075.

DNA-damage induced differentiation of leukemic cells as an anticancer barrier.
Santos M, Faryabi R, Ergen A, Day A, Malhowski A, Canela A, Onozawa M, Lee J, Callen E, Gutierrez-Martinez P, Chen H, Wong N, Finkel N, Sharrow S, Rossi D, Ito K, Ge K, Aplan P, Armstrong SA, Nussenzweig A.
Nature. 2014 Oct 2;514(7520):107-11. PMID: 25079327.

ENL links histone acetylation to oncogenic gene expression in AML.
Wan L, Wen H, Li Y, Lyu J, Hoshii T, Joseph J, Wang X, Loh Y, Erb M, Souza A, Bradner J, Shen L, Li W, Li H, Allis D, Armstrong SA, Shi X.
Nature 2017 Mar 9;543(7644):265-269. PMID: 28241141.


Our laboratory identified the histone 3 lysine 79 (H3K79) methyltransferase, DOT1L as critical for the control of leukemogenic Hox gene expression in multiple subtypes of leukemia. We contributed to the development of new small molecule DOT1L inhibitors that are the first histone methyltransferase inhibitors to be tested in humans and have expanded our focus to a number of different histone modifying enzymes as potential therapeutic opportunities in leukemia and other cancers.

H3K79 methylation profiles define murine and human MLL-AF4 leukemias.
Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU, Xia X, Jesneck J, Bracken AP, Silverman LB, Kutok JL, Kung AL, Armstrong SA.
Cancer Cell. 2008 Nov 4; 15(5):355-68. PMID: 18977325.

MLL-rearranged Leukemia is Dependent on Aberrant H3K79 Methylation by DOT1L.
Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, Pollock RM, Richon VM, Kung AL, Armstrong SA.
Cancer Cell 2011, Jul 12;20(1)66-78. PMID: 21741597.

DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia.
Chen CW, Koche RP, Sinha AU, Deshpande AJ, Zhu N, Eng R, Doench JG, Xu H, Chu SH, Qi J, Wang X, Delaney C, Bernt KM, Root DE, Hahn WC, Bradner JE, Armstrong SA.
Nature Medicine. 2015 Apr; 21(4):335-43. PMID: 25822366.

NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis.
Xu H, Valerio DG, Eisold ME, Sinha A, Koche RP, Hu W, Chen CW, Chu SH, Brien GL, Park CY, Hsieh JJ, Ernst P, Armstrong SA.
Cancer Cell. 2016 Dec 12;30(6):863-878. PMID: 27889185.


A complete list of publications can be viewed here.