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The cure rate for pediatric patients with B precursor acute lymphoblastic leukemia (pre-B ALL) is steadily improving, however relapses do occur despite...
Outcomes for infants diagnosed under 1 year of age with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have remained stagnant over the past 20 years. Successive treatment protocols have previously focused on intensification of conventional chemotherapy, but increased treatment-related toxicity and chemoresistance have led to a plateau in survival.
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.
Laurence Rishi S. Sébastien Cheung Kotecha Malinge BPharm (Hons) MBA PhD MB ChB (Hons) MRCPCH FRACP PhD PhD Co-Head, Leukaemia Translational Research
Rishi S. Laurence Sébastien Kotecha Cheung Malinge MB ChB (Hons) MRCPCH FRACP PhD BPharm (Hons) MBA PhD PhD Co-Head, Leukaemia Translational Research
B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection.
KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia.
Acute leukaemia is the most common childhood malignancy. Almost all cases are classified as acute lymphoblastic leukaemia or acute myeloid leukaemia. Acute leukaemia of ambiguous lineage (ALAL) is a rare form of acute leukaemia that cannot be classified by a single lineage. Like other acute leukaemias, ALAL typically presents with nonspecific symptoms such as fatigue, fever, or bleeding.
Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome.
Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents.