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High Expression of NTRK1 in ETV6::RUNX1 Positive Acute Lymphoblastic Leukaemia Drives Factor Independence and Sensitivity to Larotrectinib

ETV6::RUNX1 is one of the most common recurrent genomic abnormalities in acute lymphoblastic leukaemia (ALL) and is associated with a good prognosis. High expression of NTRK1, encoding tropomyosin receptor kinase A (TrkA), confers a poor prognosis in other malignancies and may contribute to therapy resistance in patients with ETV6::RUNX1 B-ALL.

Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia

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.

Challenges and considerations for antifungal prophylaxis in children with acute myeloid leukemia

Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking.

Down syndrome-associated leukaemias: current evidence and challenges

Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS.

Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia

Rearrangement of the mixed-lineage leukemia gene (MLL) is found in 80% of infant acute lymphoblastic leukemia (ALL) and is associated with poor prognosis and re

Silencing of TESTIN by dense biallelic promoter methylation

Aberrant promoter DNA methylation has been reported in childhood acute lymphoblastic leukaemia and has the potential to contribute to its onset and outcome

Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study

Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive...

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms.

Effective adenovirus-mediated gene transfer into neural stem cells derived from human embryonic stem cells

Human embryonic stem cell-derived neural stem cells (hESC-NSCs) are an attractive cell type for studying

MEIS proteins as partners of the TLX1/HOX11 oncoprotein

Aberrant expression of the TLX1/HOX11 proto-oncogene is associated with a significant subset of T-cell acute lymphoblastic leukemias...