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Lessons from 50 years of curing childhood leukaemia

One of the great success stories of modern medicine is undoubtedly the remarkable improvement in outcome for childhood cancer, achieved through the work of...

Effective targeting of the P53-MDM2 axis in preclinical models of infant MLL-rearranged acute lymphoblastic leukemia.

This study describes the development and molecular characterization of a panel of patient-derived infant leukemia oncogene xenografts and their sensitivity...

Germ-line and somatic DICER1 mutations in pineoblastoma

This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility...

A pre-clinical model of resistance to induction therapy in pediatric acute lymphoblastic leukemia

Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell...

Comparative drug screening in NUT midline carcinoma

The NUT midline carcinoma (NMC) is a rare but fatal cancer for which systematic testing of therapy options has never been performed.

Bioenergetic modulation overcomes glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia

Drug-resistant forms of acute lymphoblastic leukaemia (ALL) are a leading cause of death from disease in children.

The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution

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.

Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic 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.

Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome

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.