1. Dino Masic
Newcastle University, Northern Institute of Cancer
Research, Newcastle upon Tyne, England
Host Institute: Cincinnati Children’s Hospital, Cincinnati,
Ohio, USA
Dates of visit: 10 March – 1 September 2014
Developing a disease model for IGH-CEBPD B-cell
precursor acute lymphoblastic leukaemia.
leukaemia patients has improved outcome through
translocations of the Immunoglobulin Heavy Chain locus
Genes juxtaposed to IGH are strongly over expressed
due to powerful enhancer elements which lead to aberrant
gene function and oncogenesis. This subgroup comprises
are with the CEBP gene family. This family is comprised
regulators in a broad range of tissues, including myeloid,
adipose, liver, bone and breast. All CEBP genes, with the
Their consistent presence within a lymphoid leukaemia is
intriguing due to their known action in myeloid cell lineage
commitment, proliferation and differentiation; this is one of
the questions that we want to answer.
genomic screens to investigate both known and novel copy
number alterations. These data were used to develop the
functional branch of the project, which aims to recreate
blood and transfected with a retroviral vector containing
partner. This transduction mimics the patient phenotype via
genetic insults are required to initiate leukaemogenesis, a
an important regulator of haematological differentiation.
This deletion, resulting in the expression of the dominant
negative protein, was found to be the second most
cohort.
To facilitate this project I travelled to Cincinnati Ohio to
Children’s Hospital. The Mulloy group have successfully
createdseveraldiseasemodelsforacutemyeloidleukaemia,
transduction has greatly advanced my project. Cord blood
technology. Cell counts were performed to track population
numbers and cytospin slides were created to observe
cellular morphology.
observed in patients. While in Cincinnati I was also able
to make use of animal facilities to engraft transduced cells
material for downstream applications such as RNA
cells showed mixed lymphoid and myeloid lineages and were
These populations will be used for comparative analysis,
and may help us answer the question behind cell lineage
on the developmental mechanisms behind this leukaemia
subtype.
I would like to thank European Association for Cancer
Research for giving me the opportunity to travel to Cincinnati
and learn a number of valuable new techniques, which I am
now integrating into my group in Newcastle. I would also like
support and guidance.