Understanding and Averting Blood Cancer Resistance to Therapy

A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo

ST Diepstraten, Y Deng, MA Potts, A Heidersbach, C König, KM Dorighi, L Tai, AJ Kueh, L Whelan, C Chang, F Brown, GL Kelly, JP Fortin, B Haley, JE La Marca, MJ Herold

2026-09-18

CRISPR activation (CRISPRa) enables precise up-regulation of gene expression for ex vivo and in vivo applications. However, a lack..

Venetoclax and ibrutinib induces durable clinical responses in marginal zone lymphoma

SM Handunnetti, A Khot, P Blombery, K Burbury, PA Thompson, D Ritchie, RJ Hicks, G Burke, R Koldej, M Bressel, J Di Iulio, DA Westerman, S Lade, AW Roberts, JF Seymour, CS Tam, MA Anderson

2026-03-10

Oral ibrutinib and venetoclax (I+V) demonstrate activity as monotherapy in marginal zone lymphoma (MZL), with low complete respons..

Measurable residual disease intervention in AML: a new therapeutic horizon

AH Wei, HJ Iland, CD DiNardo, J Reynolds

2026-01-01

Acute myeloid leukemia (AML) is a polyclonal malignancy marked by high relapse rates despite initial morphologic remission. Althou..

Myeloid/lymphoid neoplasms with eosinophilia and ZMYM2::FLT3 fusion: clinical, pathological and molecular clues to a cryptic diagnosis

I Caldwell, S Grigg, L Berkahn, I Goncalves, AW Roberts, P Blombery, IS Tiong

2026-01-01

MNT: a new target for AML

KC Fischer, V Litalien, ST Diepstraten, M Jahja, FC Brown, GL Kelly, AH Wei, S Cory

2025-11-01

Deregulated expression of the transcription factor c-MYC is well established as a primary driver of diverse tumor types. In this s..

Emergent BAX-mutated clonal hematopoiesis after venetoclax-based therapy for breast cancer

IS Tiong, T Nguyen, CC Chua, CE Teh, C Muttiah, S Ftouni, JF Seymour, D Gray, AW Roberts, SJ Dawson, GJ Lindeman, P Blombery

2025-09-09

Final analysis of the phase 1b Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT)

CC Chua, S Loo, CY Fong, SB Ting, IS Tiong, S Fleming, NS Anstee, A Ivey, M Ashby, TC Teh, J Reynolds, AW Roberts, AH Wei

2025-04-22

Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML). The Chemotherapy..

Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes

H Peng, JS Jabbari, L Tian, C Wang, Y You, CC Chua, NS Anstee, N Amin, AH Wei, NM Davidson, AW Roberts, DCS Huang, ME Ritchie, R Thijssen

2025-04-01

Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. ..

Novel mechanisms of resistance in CLL: variant BTK mutations in second-generation and noncovalent BTK inhibitors

CS Tam, S Balendran, P Blombery

2025-03-06

Bruton tyrosine kinase inhibitors (BTKis) are an established standard of care in chronic lymphocytic leukemia. The covalent BTKis ..

Breathing new insights into the role of mutant p53 in lung cancer

T Chen, LM Ashwood, O Kondrashova, A Strasser, G Kelly, KD Sutherland

2025-02-03

The tumour suppressor gene p53 is one of the most frequently mutated genes in lung cancer and these defects are associated with po..

Genomic mechanisms associated with resistance to PDL1-blockade in a patient with mantle cell lymphoma

S Grigg, S Lade, G Ryland, S Grimmond, M Dickinson, P Blombery

2025-01-01

Don't fear the reaper: The role of regulated cell death in tumorigenesis and BH3-mimetics for cancer therapy

JE La Marca, GL Kelly, A Strasser, ST Diepstraten

2024-10-07

From its earliest characterization, it has been recognized that there is a role for regulated (programmed) cell death in cancer. A..

Mouse models to investigate in situ cell fate decisions induced by p53

E Lieschke, AF Thomas, A Kueh, GK Atkin-Smith, PL Baldoni, JE La Marca, S Young, AS Huang, AM Ross, L Whelan, D Kaloni, L Tai, GK Smyth, MJ Herold, ED Hawkins, A Strasser, GL Kelly

2024-10-01

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised a..

Potential impact of NOTCH1 activation on venetoclax sensitivity in chronic lymphocytic Leukaemia: In vitro insights and clinical implications

MY Gao, A Georgiou, VS Lin, M Jahja, CA White, MA Anderson, MP McCormack, AW Roberts, DCS Huang, R Thijssen

2024-10-01

Despite significant progress in treating chronic lymphocytic leukaemia (CLL), resistance to therapy remains challenging. NOTCH1 ac..

Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions

SM Handunnetti, MA Anderson, K Burbury, PA Thompson, G Burke, M Bressel, J Di Iulio, RJ Hicks, D Westerman, S Lade, C Pott, R Agarwal, R Koldej, D Ritchie, M Dreyling, MA Dawson, SJ Dawson, JF Seymour, AW Roberts, CS Tam

2024-08-22

In the phase 2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refracto..

Response and Resistance to Menin Inhibitor in UBTF–Tandem Duplication AML

IS Tiong, DS Ritchie, P Blombery

2024-06-27

Tandem duplication in UBTF is associated with a resistant form of AML. A menin inhibitor induced a short-lived response. Resistanc..

Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers

ST Diepstraten, Y Yuan, JE La Marca, S Young, C Chang, L Whelan, AM Ross, KC Fischer, G Pomilio, R Morris, A Georgiou, V Litalien, FC Brown, AW Roberts, A Strasser, AH Wei, GL Kelly

2024-05-13

TP53-mutant blood cancers remain a clinical challenge. BH3-mimetic drugs inhibit BCL-2 pro-survival proteins, inducing cancer cell..

Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses

JE La Marca, BJ Aubrey, B Yang, C Chang, Z Wang, A Kueh, L Tai, S Wilcox, L Milla, S Heinzel, D Vremec, L Whelan, C König, D Kaloni, AK Voss, A Strasser, ST Diepstraten, MJ Herold, GL Kelly

2024-02-01

Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that imp..

BCL-W makes only minor contributions to MYC-driven lymphoma development

ST Diepstraten, JE La Marca, C Chang, S Young, A Strasser, GL Kelly

2023-09-08

The BH3-mimetic drug Venetoclax, a specific inhibitor of anti-apoptotic BCL-2, has had clinical success for the treatment of chron..

Lymphoma cells lacking pro-apoptotic BAX are highly resistant to BH3-mimetics targeting pro-survival MCL-1 but retain sensitivity to conventional DNA-damaging drugs

ST Diepstraten, S Young, JE La Marca, Z Wang, RM Kluck, A Strasser, GL Kelly

2023-04-01

BH3-mimetic drugs are an anti-cancer therapy that can induce apoptosis in malignant cells by directly binding and inhibiting pro-s..

BCL-2 protein family: attractive targets for cancer therapy

D Kaloni, ST Diepstraten, A Strasser, GL Kelly

2023-02-01

Acquired resistance to cell death is a hallmark of cancer. The BCL-2 protein family members play important roles in controlling ap..

Enrichment of BTK Leu528Trp mutations in patients with CLL on zanubrutinib: potential for pirtobrutinib cross-resistance

P Blombery, ER Thompson, TE Lew, IS Tiong, R Bennett, CY Cheah, KL Lewis, SM Handunnetti, CPS Tang, A Roberts, JF Seymour, CS Tam

2022-10-25

The covalent Bruton’s tyrosine kinase inhibitors (BTKis) are highly effective for the treatment of chronic lymphocytic leukemia (C..