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B lymphopoiesis is characterized by progressive loss of multipotent potential in hematopoi-etic stem cells, followed by commitment to differentiate into B cells, which mediate the humoral response of the adaptive immune system.
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.
Osteoporosis is a chronic skeletal condition characterized by low bone mass and deteriorated microarchitecture of bone tissue and puts tens of millions of people at high risk of fractures. New therapeutic agents like i-bodies, a class of next-generation single-domain antibodies, are needed to overcome some limitations of conventional treatments.
Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required.
T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10-20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing.
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.
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.
Rishi S. Kotecha MB ChB (Hons) MRCPCH FRACP PhD Co-Head, Leukaemia Translational Research rishi.kotecha@health.wa.gov.au Co-Head, Leukaemia
Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children's Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy.
Patients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics.