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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.
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.
Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy and remains one of the most common causes of cancer-related death in children and adolescents. Five-year overall survival rates now exceed 90% with current multidrug chemotherapeutic regimens.
Extensive research over the past 50 years has resulted in significant improvements in survival for patients diagnosed with leukemia. Despite this, a subgroup of patients harboring high-risk genetic alterations still suffer from poor outcomes. There is a desperate need for new treatments to improve survival, yet consistent failure exists in the translation of in vitro drug development to clinical application.
PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach.
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.
Rishi S. Kotecha MB ChB (Hons) MRCPCH FRACP PhD Co-Head, Leukaemia Translational Research rishi.kotecha@health.wa.gov.au Co-Head, Leukaemia
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.