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Preclinical Assessment of Dactinomycin in KMT2A-Rearranged Infant Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have high rates of relapse and poor survival compared with children. Few new therapies have been identified over the past twenty years. The aim of this study was to identify existing anti-cancer agents that have the potential to be repurposed for the treatment of infant ALL.

Interleukin-4 modulates type I interferon to augment antitumor immunity

Despite advances in immunotherapy, metastatic melanoma remains a considerable therapeutic challenge due to the complexity of the tumor microenvironment. Intratumoral type I interferon (IFN-I) has long been associated with improved clinical outcomes. However, several IFN-I subtypes can also paradoxically promote tumor growth in some contexts. 

Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer

Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions.

The ETO2 transcriptional cofactor maintains acute leukemia by driving a MYB/EP300-dependent stemness program

Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well-established repressive activity, ETO2 directly activates transcription of MYB, among other genes.

Romidepsin enhances the efficacy of cytarabine in vivo, revealing HDAC inhibition as a therapeutic strategy for KMT2A-rearranged acute lymphoblastic leukemia

In this study, we investigate the in vivo synergy between romidepsin and cytarabine

Partial trisomy 21 contributes to T-cell malignancies induced by JAK3-activating mutations in murine models

This JAK3A572V knockin model is a relevant new tool for testing the efficacy of JAK inhibitors in JAK3-related hematopoietic malignancies

Development of new preclinical models of childhood leukaemia

Sébastien Laurence Rishi S. Malinge Cheung Kotecha PhD BPharm (Hons) MBA PhD MB ChB (Hons) MRCPCH FRACP PhD Laboratory Head, Translational Genomics

Exploring clonal diversity in paediatric B-cell leukaemia to identify new therapeutic weakness

Sébastien Rishi S. Laurence Timo Malinge Kotecha Cheung Lassmann PhD MB ChB (Hons) MRCPCH FRACP PhD BPharm (Hons) MBA PhD BSc (Hons) MSc PhD

Targeting DYRK1A: a key player in Down syndrome Leukaemogenesis

Sébastien Malinge PhD Laboratory Head, Translational Genomics in Leukaemia, Senior Research Fellow (University of Western Australia), Adjunct Senior

Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required.