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Therapeutic opportunities from dissecting the pre-B leukaemia bone marrow microenvironmentLaurence Rishi S. Sébastien Cheung Kotecha Malinge BPharm (Hons) MBA PhD MB ChB (Hons) MRCPCH FRACP PhD PhD Co-Head, Leukaemia Translational Research
The main aim of our Leukaemia Translational Research Team is to test innovative therapeutic approaches, with a focus on clinical translation of this knowledge, to improve the outcomes of children suffering from leukaemia.
Research
Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell LeukemiaChildren 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).
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Updates in infant acute lymphoblastic leukemia and the potential for targeted therapyOutcomes for infants diagnosed under 1 year of age with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have remained stagnant over the past 20 years. Successive treatment protocols have previously focused on intensification of conventional chemotherapy, but increased treatment-related toxicity and chemoresistance have led to a plateau in survival.
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Systematic In Vitro Evaluation of a Library of Approved and Pharmacologically Active Compounds for the Identification of Novel Candidate Drugs for KMT2A-Rearranged LeukemiaPatients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics.
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High expression of connective tissue growth factor accelerates dissemination of leukaemiaFunctional role of CTGF in altering disease progression in a lymphoid malignancy
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Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesisHematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell...
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Comparative drug screening in NUT midline carcinomaThe NUT midline carcinoma (NMC) is a rare but fatal cancer for which systematic testing of therapy options has never been performed.
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Preclinical Assessment of Dactinomycin in KMT2A-Rearranged Infant Acute Lymphoblastic LeukemiaInfants 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.
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Polyamine depletion limits progression of acute leukaemiaCancer 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.