Search
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.
Mesothelioma is a cancer derived from mesothelial cells, most commonly arising from the pleura or the peritoneum. Immune checkpoint therapy (ICT) has shown survival benefit for pleural mesothelioma, but little is known about the response in peritoneal mesothelioma. Most preclinical mesothelioma models involve subcutaneous cancer cell implantation, which lacks the relevant tumour microenvironment of peritoneal mesothelioma and does not resemble the clinical presentation.
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.
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.
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.
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.
Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome.