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Showing results for "rishi kotecha"
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.
Nick Rishi S. Laurence Sung Gottardo Kotecha Cheung Chiu MBChB FRACP PhD MB ChB (Hons) MRCPCH FRACP PhD BPharm (Hons) MBA PhD MBBS FRACP FRCPA PhD
Allogeneic hematopoietic stem cell transplant (HSCT) is a proven curative therapy for children with high-risk myeloid malignancies. Disease relapse, transplant-related mortality and graft versus host disease (GvHD) are the main causes of treatment failure and death post-transplant. The optimum pretransplant conditioning regimen is yet to be defined. There is limited data regarding the use of busulfan, fludarabine and melphalan as a myeloablative conditioning regimen in children receiving HSCT for myeloid malignancies.
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 now well accepted that germline or de novo genetic alterations predispose to cancer development, especially during childhood. Among them, constitutive trisomy 21, also known as Down syndrome (DS), has been shown to predispose to acute leukemia affecting both the myeloid (ML-DS) and lymphoid (DS-ALL) lineages. ML-DS is associated with a good prognosis compared to children without DS, due in part to a higher sensitivity to conventional chemotherapy.
Patients 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.
In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells.
Investigation of this rare mixed lineage leukemia cytogenetic abnormality aims to provide further evidence of the genetic changes that underpin this leukemia.
Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.
Structural and numerical alterations of chromosome 21 are extremely common in hematological malignancies. While the functional impact of chimeric transcripts from fused chromosome 21 genes such as TEL-AML1, AML1-ETO, or FUS-ERG have been extensively studied, the role of gain of chromosome 21 remains largely unknown.