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Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.
The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.
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.
Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are...
Connective tissue growth factor (CTGF/CCN2) has been shown previously to be aberrantly expressed in a high proportion of paediatric precursor B cell acute...
One of the great success stories of modern medicine is undoubtedly the remarkable improvement in outcome for childhood cancer, achieved through the work of...
This study describes the development and molecular characterization of a panel of patient-derived infant leukemia oncogene xenografts and their sensitivity...
This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility...
Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem.
Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell...