Disease relapse is a major barrier to long-term remission in AML and is attributed to the presence of measurable residual disease (MRD). MRD assessment is established for prognostication and therapeutic guidance in AML, but only a handful of MRD markers are currently recognized for this purpose. We aim to validate the prognostic impact of novel MRD markers and assays and gain further insight into what drives resistance in these MRD cells using single cell technologies. Additionally, we have established a world first multi-domain, adaptive platform trial, ALLG AMLM26: INTERCEPT, which aims to facilitate the proof-of-concept development of new therapies and combinations for patients with increasing MRD in AML according to the MRD biomarker present.

Prof Andrew Wei, Lab Head | WEHI Researcher Profile

Q: Employing novel technologies to improve clinical activity of targeted therapies in AML

Patients with TP53 aberrations or FLT3-ITD+ AML have a particularly high risk for relapse and resistance to therapy. This project uses innovative proteomic and biochemical techniques to analyse protein expression and activity in these high-risk subgroups of AML. This project aims to identify changes in immune signatures that may indicate which patients are likely to fail treatment and provide a list of potential new therapeutic targets. Analysis of serial patient samples culminating in treatment failure will also allow for identification of proteins most relevant to the drug resistant phenotype in addition to any changes that could be leveraged to improve patient outcomes.

About

Professor Andrew Wei is a clinical haematologist, haematopathologist, National Health and Medical Research Council (NHMRC) investigator (2023-2027), Metcalf Family Fellow and laboratory head in the Blood Cells and Blood Cancers division.

The focus of the lab is to develop and conduct clinical trials for patients with acute myeloid leukaemia (AML) and conduct investigations into mechanisms of resistance to novel AML therapies. The lab also has an active role in validating new drugs and combinations for future clinical development in the field of AML.

The Wei Lab has spent over a decade working with primary patient samples and developing patient xenograft models to study the disease. A new focus of the lab is to study the mechanisms involved in the evolution TP53 mutated cells into AML and to investigate novel treatment possibilities aimed at improving therapeutic outcomes for this poor risk patient population.

The lab is supported by research funding from NHMRC, MRFF and various industry collaborations.

Education

Joint appointments

Grants and funding

Publications

Selected publications from Prof Andrew Wei

Loo S, Potter N, Ivey A, O’Nions J, Moon R, Jovanovic J, Fong CY, Anstee NS, Tiong IS, Othman J, Chua CC, Renshaw H, Baker R, Fleming S, Russell NH, Ritchie D, Bajel A, Hou H-A, Dillon R, Wei AH. Pretransplant MRD detection of fusion transcripts is strongly prognostic in KMT2A-rearranged acute myeloid leukemia. Blood. 2024;144(24):10.1182/blood.2024026605

Tiong IS, Hiwase DK, Abro E, Bajel A, Palfreyman E, Beligaswatte A, Reynolds J, Anstee N, Nguyen T, Loo S, Chua CC, Ashby M, Wiltshire KM, Fleming S, Fong CY, Teh T-C, Blombery P, Dillon R, Ivey A, Wei AH. Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC). Journal of Clinical Oncology. 2024;42(18):10.1200/jco.23.01599

Loo S, Roberts AW, Anstee NS, Kennedy GA, He S, Schwarer AP, Enjeti AK, D’Rozario J, Marlton P, Bilmon IA, Taper J, Cull G, Tiley C, Verner E, Hahn U, Hiwase DK, Iland HJ, Murphy N, Ramanathan S, Reynolds J, Ong DM, Tiong IS, Wall M, Murray M, Rawling T, Leadbetter J, Rowley L, Latimer M, Yuen S, Ting SB, Fong CY, Morris K, Bajel A, Seymour JF, Levis MJ, Wei AH, Group ALAL. Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG. Blood. 2023;142(23):10.1182/blood.2023020301

Moujalled DM, Brown FC, Chua CC, Dengler MA, Pomilio G, Anstee NS, Litalien V, Thompson ER, Morley TD, MacRaild S, Tiong IS, Morris R, Dun K, Zordan AC, Shah JS, Banquet S, Halilovic E, Morris EJ, Herold MJ, Lessene GL, Adams JM, Huang DCS, Roberts AW, Blombery P, Wei AH. Acquired mutations in BAX confer resistance to BH3-mimetic therapy in Acute Myeloid Leukemia. Blood. 2023;141(6):10.1182/blood.2022016090

Loo S, Dillon R, Ivey A, Anstee NS, Othman J, Tiong IS, Potter N, Jovanovic J, Runglall M, Chua CC, Bajel A, Ritchie DS, Gray K, Yeoh ZH, McBean M, Gilkes AF, Thomas I, Johnson S, Russell NH, Wei AH. Pre-transplant FLT3-ITD MRD assessed by high-sensitivity PCR-NGS determines post-transplant clinical outcome. Blood. 2022;140(22):10.1182/blood.2022016567

Thijssen R, Diepstraten ST, Moujalled D, Chew E, Flensburg C, Shi MX, Dengler MA, Litalien V, MacRaild S, Chen M, Anstee NS, Reljić B, Gabriel SS, Djajawi TM, Riffkin CD, Aubrey BJ, Chang C, Tai L, Xu Z, Morley T, Pomilio G, Bruedigam C, Kallies A, Stroud DA, Bajel A, Kluck RM, Lane SW, Schoumacher M, Banquet S, Majewski IJ, Strasser A, Roberts AW, Huang DCS, Brown FC, Kelly GL, Wei AH. Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias. Blood. 2021;137(20):10.1182/blood.2020010167

Chua CC, Roberts AW, Reynolds J, Fong CY, Ting SB, Salmon JM, MacRaild S, Ivey A, Tiong IS, Fleming S, Brown FC, Loo S, Majewski IJ, Bohlander SK, Wei AH. Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy.Journal of Clinical Oncology. 2020;38(30):10.1200/jco.20.00572

DiNardo CD, Tiong IS, Quaglieri A, MacRaild S, Loghavi S, Brown FC, Thijssen R, Pomilio G, Ivey A, Salmon JM, Glytsou C, Fleming SA, Zhang Q, Ma H, Patel KP, Kornblau SM, Xu Z, Chua CC, Chen X, Blombery P, Flensburg C, Cummings N, Aifantis I, Kantarjian H, Huang DCS, Roberts AW, Majewski IJ, Konopleva M, Wei AH. Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood. 2020;135(11):10.1182/blood.2019003988

Moujalled DM, Pomilio G, Ghiurau C, Ivey A, Salmon J, Rijal S, Macraild S, Zhang L, Teh T-C, Tiong I-S, Lan P, Chanrion M, Claperon A, Rocchetti F, Zichi A, Kraus-Berthier L, Wang Y, Halilovic E, Morris E, Colland F, Segal D, Huang D, Roberts AW, Maragno AL, Lessene G, Geneste O, Wei AH. Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia. Leukemia. 2019;33(4):10.1038/s41375-018-0261-3

Boyiadzis M, Wei AH, Paiva B, Freeman SD, Kaspers G, Chyla B, Hersey S, Patel R, Maloney B, Zumofen MB, Van Hoef M, Wulff B, Obourn V, Patel S, de Menezes DL, Shi Q, Bengoudifa B, Dimier N, Prior TJ, Roboz GJ, Prebet T. Measurable residual disease (MRD) as a surrogate end point for clinical drug approval in acute myeloid leukemia (AML): Perspectives from the MRD Partnership and Alliance in AML Clinical Treatment Consortium. Cancer. 2025;131(13):10.1002/cncr.35960