Dickins Group - AML

Key terms

Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Tumour suppressor genes, Transcription factors, Differentiation therapy

2022 Dickins group
2022 group L-R: Ms Veronica Voo, Mr Jake Tremewen, Ms Stephanie Wiranata, Ms Samin Iranfar, Dr Ethan Oxley, Associate Professor Ross Dickins.

Group Leader

Research Overview

The Dickins laboratory at the Australian Centre for Blood Diseases examines what causes leukaemia and how its treatment may be improved. In collaboration with scientific and clinical colleagues at ACBD, across Melbourne, and worldwide, we build and analyse new models of leukemia development and therapy. We aim to understand how recurrent oncogenic mutations influence the behaviour of normal and malignant cells, and how these changes in leukaemia cells may be exploited to therapeutic advantage. We also study how myeloid  lineage antigen-presenting cells regulate T cell costimulation in autoimmunity and cancer.

Research Interests

The body produces over 100 billion white blood cells daily, requiring massive proliferation of immature progenitor cells in the bone marrow. Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are caused by genetic mutations that block progenitor maturation, locking them in a state of perpetual proliferation. Our laboratory examines therapeutic strategies that re-engage leukemia cell differentiation and natural mechanisms of mature cell clearance. We use reversible RNAi, CRISPR, and other genetic technologies to generate custom leukemia models that recapitulate the genetics of human leukemia, and test novel therapeutic strategies in established leukemias in mice.

Funding

Our laboratory is funded by the Australian Government National Health and Medical Research Council and the Mark Foundation for Cancer Research. Previously we have received funding from the Leukaemia Foundation of Australia, the Sylvia and Charles Viertel Charitable Foundation, veski, and Australian Rotary Health.

Selected Publications

Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy. Ngo S, Oxley EP, Ghisi M, Garwood MM, McKenzie MD, Mitchell HL, Kanellakis P, Susanto O, Hickey MJ, Perkins AC, Kile BT, Dickins RA. Nat Commun 12, 6546 (2021).

Interconversion between tumorigenic and differentiated states in acute myeloid leukemia. McKenzie MD*, Ghisi M*, Oxley EP*, Ngo S, Cimmino L, Esnault C, Liu R, Salmon JM, Bell CC, Ahmed N, Erlichster M, Witkowski MT, Liu GJ, Chopin M, Dakic A, Simankowicz E, Pomilio G, Vu T, Krsmanovic P, Su S, Tian L, Baldwin TM, Zalcenstein DA, DiRago L, Wang S, Metcalf D, Johnstone RW, Croker BA, Lancaster GI, Murphy AJ, Naik SH, Nutt SL, Pospisil V, Schroeder T, Wall M, Dawson MA, Wei AH, De The H, Ritchie ME, Zuber J, Dickins RA. Cell Stem Cell 25, 258-272 (2019). *equal contributors

Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski MT, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Torres Martin M, Guillamot M, Bahn RS, Xu M, Figueroa ME, Dickins RA, Abdel-Wahab O, Park CY, Tsirigos A, Neel BG, Aifantis I. Cell 170, 1079-1095 (2017).

Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome. Witkowski MT, Hu Y, Roberts KG, Boer JM, McKenzie MD, Liu GJ, Le Grice OD, Tremblay CS, Ghisi M, Willson TA, Horstmann MA, Aifantis I, Cimmino L, Frietze S, den Boer ML, Mullighan CG, Smyth GK, Dickins RA. J Exp Med 214, 773-791 (2017).

Activated Notch signaling counteracts Ikaros tumor suppression in mouse and human T cell acute lymphoblastic leukemia. Witkowski MT*, Cimmino L*, Hu Y, Trimarchi T, Tagoh H, McKenzie MD, Best SA, Tuohey L, Willson TA, Nutt SL, Busslinger M, Aifantis I, Smyth GK, Dickins RA. Leukemia 29, 1301-1311 (2015). *equal contributors

Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia. Liu GJ, Cimmino L, Jude JG, Hu Y, Witkowski MT, McKenzie MD, Kartal-Kaess M, Best SA, Tuohey L, Mullighan CG, Farrar MA, Nutt SL, Smyth GK, Zuber J, Dickins RA. Genes Dev 28, 1337-1350 (2014).

Tissue-specific and reversible RNA interference in transgenic mice. Dickins RA, McJunkin K, Hernando E, Premsrirut PK, Krizhanovsky V, Burgess DJ, Kim SY, Cordon-Cardo C, Zender L, Hannon GJ, Lowe SW. Nat Genet 39, 914-921 (2007).

Probing tumor phenotypes using stable and regulated synthetic microRNA precursors. Dickins RA, Hemann MT, Zilfou JT, Simpson DR, Ibarra I, Hannon GJ, Lowe SW. Nat Genet 37, 1289-1295 (2005).

Dickins Lab Alumni

Steven Ngo (PhD 2016-19, Postdoc 2019-21) London, UK

Skye Ho (Hons 2020) Melbourne

Jade Jowett-Crociani (Hons 2020) Melbourne

Ariel Lebenbaum (Hons 2019) Melbourne

Jacqueline Rusnak (Hons 2019) Melbourne

Thao Nguyen (Postdoc 2018) Melbourne

Swathy Jayakrishnan (Hons 2018) Rome, Italy

Margherita Ghisi (Postdoc 2014-15) Toulouse, France

Tina Vu (Hons 2017) Sydney

Emilia Simankowicz (RA 2015-18) Melbourne

Minhee Halemba (RA 2014-15) Melbourne

Michael Erlichster (Hons 2013) Melbourne

Mutlu Kartal-Kaess (Postdoc 2010-13) Bern, Switzerland

Matthew Witkowski (Hons 2011, PhD 2012-15) Aurora, Colorado

Mark McKenzie (Postdoc 2010-15) Melbourne

Laura Tuohey (RA 2010-11) Melbourne

Luisa Cimmino (Postdoc 2008-11) Miami, Florida

Megumi Takiguchi (Postdoc 2009-12) Perth

Grace Liu (PhD 2010-14) Vienna, Austria

Rachael Lane (RA 2008-12) Melbourne

Sarah Best (RA 2008, Hons 2009) Melbourne