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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.

Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179

OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies to target this tumor cell population.

Polyamine depletion limits progression of acute leukaemia

Cancer cells are addicted to polyamines, polycations essential for cellular function. While dual targeting of cellular polyamine biosynthesis and polyamine uptake is under clinical investigation in solid cancers, preclinical and clinical studies into its potential in haematological malignancies are lacking. Here we investigated the preclinical efficacy of polyamine depletion in acute leukaemia.

It is more “unbalanced” than you think

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

Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell Leukemia

Children with Down syndrome (constitutive trisomy 21) that develop acute lymphoblastic leukemia (DS-ALL) have a 3-fold increased likelihood of treatment-related mortality coupled with a higher cumulative incidence of relapse, compared with other children with B-cell acute lymphoblastic leukemia (B-ALL).

Targeting cytokine- and therapy-induced PIM1 activation in preclinical models of T-cell acute lymphoblastic leukemia and lymphoma

IL7 and glucocorticoids coordinately drive aberrant activation of PIM1 and suggests that T-ALL and T-LBL patients could benefit from PIM inhibition

Challenges posed by COVID-19 to children with cancer

Development of standardised guidance by national and regional authorities for reducing the risk of SARS-CoV-2 transmission to children with cancer

Germline Elongator mutations in Sonic Hedgehog medulloblastoma

Genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers

Successful treatment of a child with acute monoblastic leukaemia who relapsed with T-cell acute lymphoblastic leukaemia: A rare lineage switch

Rishi S. Kotecha MB ChB (Hons) MRCPCH FRACP PhD Co-Head, Leukaemia Translational Research rishi.kotecha@health.wa.gov.au Co-Head, Leukaemia

PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein

Our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis