Multiple Myeloma Research – Dr Karen Shires
Dr Karen Shires
Medical Scientist, Division of Haematology, University of Cape Town Medical School
Title of the project
Cancer/Testis antigen expression in Multiple Myeloma
- Aim of the project
- What has been achieved to date?
- What do you hope to achieve in the next year?
Aim of the project
The aim of this study is two fold. Firstly, we want to start to investigate the use of a MM-specific CTA gene expression panel as a means of determining high risk/poor prognosis patients. Secondly, we will use the CTA panel to try to identify the “malignant” cell population and thereby help elucidate disease pathogenesis.
Several objectives will be addressed to achieve these aims:
- Development of the following CTA panel: BAGE, LAGE, MAGE (C1 and A3/6), SpanXb, PRAME, PAGE, NYESO-1, GAGE, SSX-2, where gene expression can be simultaneously analysed in each patient sample.
- Analyse the association between CTA expression and the following prognostic factors: hyperdiploidy; plasma cell proliferation index; major MM associated translocations (involving chromosome 14); chromosome 13 deletions.
- Identify the cell population/s that are expressing these CTA genes (i.e: CD138+, CD138-)
What has been achieved to date?
This project was started in April 2010. So far, the student has mastered the PCRtechniques required to analyse CTA expression in MM patients. The CTA PCR panel is almost complete, with MAGE analysis being the only outstanding reaction to configure. The student has also completed the project proposal required for registration in our division and has handed this in for approval.
Reagents required for the analysis of the proliferation index: Ki-67 and CD138 antibodies, have been ordered and we will be assisted with this analysis by Dr Dirk Lang (UCT), using fluorescence microscopy. Ms Daphne Hayward (NHLS, cytogenetics unit) has also agreed to collaborate in the analysis of the cytogenetic abnormalities and we are in the process of deciding which probes must be purchased.
While awaiting reagents, new myeloma samples are being batched as fixed slides and RNA extracts, until the assays are ready to be undertaken.
What do you hope to achieve in the next year?
This year we hope to complete all of the development work for the assays and commence with the sequential analysis of all new myelomas that are being treated in the division, looking at the CTA profiles, ploidy status, proliferation index and cytogenetic abnormalities. We are hoping to be able to analyse at least 20 patients this year. Characterisation of theCTA expressing clones will only be investigated next year.