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Disruption of cotranscriptional splicing suggests that RBM39 is a therapeutic target in acute lymphoblastic leukemiaThere are few options for patients with relapse/refractory B-cell acute lymphoblastic leukemia, thus this is a major area of unmet medical need. Here, we reveal that inclusion of a poison exon in RBM39, which could be induced both by CDK9 or CDK9 independent CMGC (cyclin-dependent kinases, mitogen-activated protein kinases, glycogen synthase kinases, CDC-like kinases) kinase inhibition, is recognized by the nonsense-mediated mRNA decay pathway for degradation.
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Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease driversAcute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes.
The Translational Genomics in Leukaemia team is focused on identifying the causes of leukaemia, with the goal of developing new targeted treatments to improve quality of care and long-term survival for all children with leukaemia.
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Cancer CentreListed are all The Kids Research Institute Australia research teams involved in our Cancer Centre. This Centre sits under the Chronic and Severe Diseases research theme.
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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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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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Targeting DYRK1A: a key player in Down syndrome LeukaemogenesisSébastien Malinge PhD Laboratory Head, Translational Genomics in Leukaemia, Ursula Kees Fellow (CCRF), Cancer Council WA Fellow (CCWA), Senior
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It is more “unbalanced” than you thinkSébastien Malinge PhD Laboratory Head, Translational Genomics in Leukaemia, Ursula Kees Fellow (CCRF), Cancer Council WA Fellow (CCWA), Senior
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Stepwise GATA1 and SMC3 mutations alter megakaryocyte differentiation in a Down syndrome leukemia modelAcute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model of clonal evolution from a preleukemic transient myeloproliferative disorder requiring both a trisomy 21 (T21) and a GATA1s mutation to a leukemia driven by additional driver mutations.
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Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research SocietyResearch focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome.