Paediatric Malignancy Unit

New image1The Paediatric Malignancy Unit (PMU) is involved in several translational research projects, both in-house and with national and international research collaborators. The core facility section of PMU also supports external academic and pharmacogenomic research studies.

Current PMU laboratory research projects include:

1. The investigation of genetically unclassified childhood B-precursor acute lymphoblastic leukaemia

Subtypes of acute lymphoblastic leukaemia (ALL) are associated with acquired and specific genetic alterations in the leukaemic cells. The genetic changes identified are used to determine risk and treatment in children with ALL. Approximately 40 per cent of childhood precursor B-ALL cases lack the presence of prognostically significant genetic abnormalities; and relapses in this group of patients are common. We are currently investigating the leukaemic cells from these genetically unclassified cases for the presence of recurrent genomic changes, the aim of which is to identify new prognostic markers and to optimise treatment for this group of patients. This study is part of a PhD project and has so far yielded promising data, which was recently submitted as an abstract for presentation at the 2011 annual meeting of the prestigious American Society of Hematology.

2. Transient abnormal myelopoiesis in Down Syndrome (DS) infants

Acquired copies of chromosome 21 are commonly found in the bone marrow cells in acute leukaemia. Constitutional trisomy 21 (Down Syndrome) is associated with a strikingly increased risk for childhood leukaemia. Therefore, a potential oncogenic role for trisomy 21 is likely. A study of archived blood and bone marrow samples from a sizable number of DS infants with transient abnormal myelopoiesis (TAM), referred to Great Ormond Street Hospital (1998-2011), is ongoing. Genomic characterization of abnormal cells at a cytogenetic and molecular level, with the aim of identifying early mutational events, should add to the understanding of the underlying biology of TAM transforming to acute myeloid leukaemia.

3. Single cell analysis in minimal residual disease

After attending a single cell analysis workshop in the Cold Spring Harbor Labs, NY, a strategy is underway to conduct a pilot study using single-cell agarose encapsulation technology to isolate and characterize the resident abnormal cells in minimal residual disease (MRD). Using this technology we hope to probe the stochastic mechanisms of carcinogenesis, progression, and response to chemotherapy.

© 2011 Great Ormond Street Hospital for Children NHS Trust