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When the Unknown Patient attends these scientific meetings, often wonders why he really should be interested in some of the topics on the agenda. They often seem like they are overly theoretical and their potential connection to anything that might be of direct benefit to a patient could remain forever Unknown. Yet, the Unknown Patient is often surprised, as he was this morning, at how relevant these basic science investigations can be. There is a lot of exciting work going on in applying new discoveries in genetics and proteomics to myeloma. The progress and hope for the future was very much in evidence in this session.

Drs. John  Shaughnessy and Gareth Morgan chaired this session on "Genetic Heterogeneity in MM:  Impact on Diagnosis And Therapy."


Gene Expression Profiling: From Bench To Bedside

Dr. Shaugnessy opened the session with an exciting presentation about the application of gene arrays to multiple myeloma. Gene arrays are a relatively new technology that allows scientists to construct a microchip that will allow them to test for activation of specific genes.
This strategy allows them to "search the haystack" to find a needle, i.e., a gene or set of genes that appears to be important in development or progression of the disease or in causing organ damage related to the disease.

The picture below shows how Dr. Shaughnessy used this strategy to compare tumor samples from patients with no myeloma bone lesions to those from patients with 3 or more lesions. The result was a striking pattern suggesting that there were substantive genetic differences in tumor biology that could be important targets for new therapeutic approaches.


Two proteins were linked to the genes that were different, but only one of them was found to have any relevance to myeloma. The findings led to identification of a protein, dkk1, connected to activation of these genes, which appears to play a role in shutting down osteoblasts, which are the cells responsible for growth of bone tissue.

...And these results were confirmed by comparing the bone marrows of patients with these genes switched on and off.


Gene Expression Profiling: From Gene Expression Profiles To SNPs

Next up was Dr. Brian Van Ness. Dr. Van Ness shared the results of his work in gene expression profiling using the Affymetrix U95A GeneChip. A hierarchal clustering analysis showed six distinct groups of genes that appear to be important in myeloma.

Dr. Van Ness also discussed complementary work being undertaken to look at SNPs (single nucleotide polymorphisms) in normal tissue in both the patient population, in family members of myeloma patients and in healthy controls. This work is part of a project sponsored by the IMF and being chaired by Dr. Van Ness and Dr. Gareth Morgan.

The IMF's Bank On A Cure project represents the beginning of an international effort to establish a large DNA bank and develop a population-based study of genetic variants in myeloma.


Development Of A Myeloma-Specific Array

Dr. Keith Stewart shared elements of his work on developing a gene chip that would focus on genes thought to be important on myeloma.  Such a chip would provide a more powerful tool for myeloma research than chips developed for other diseases (e.g., lymphoma) currently being used in myeloma.


Molecular cytogenetic classification of myeloma: Cytogenetic and micro-arrays

Dr. Herves Avet-Loiseau spoke about the progress that has been made in cataloguing chromosomal abnormalities in myeloma, MGUS and related conditions. No single abnormality can identify these conditions. For example, no specific chromosmal abnormality distinguishes MGUS from myeloma. Hypodiploidy, especiall loss of 13q, is associated with poorer risk disease. However, since loss of chromosome 13 occurs in MGUS, this is clearly not the factor determining transformation to active disease.

Much more research is necessary to "pin point" the critical molecular mutations which result in growth, drug resistance and various disease patterns in patients with myeloma.


Molecular cytogenetic classification of myeloma: Clinical and Prognostic Implications

Dr. Rafael Fonseca discussed the clinical and prognostic implications of various "molecular lesions" in myeloma. These are mutation of genes in tumor cells that affect how the cells will behave and the course of the disease.


Molecular Cytogenetics of Myeloma Biology. 14 q 32 Translocations in Multiple Myeloma Patients

Dr. C. Bastard explored the significance of these molecular lesions in myeloma patients. Sorry, no further information is available on this talk.



The panel (below) fielded questions at the end of the session.



Please note that the Unknown Patient is a patient, not a doctor and not a scientist. This summary represents a layman's view of what was said at the conference and should form a basis for raising awareness of issues that could be discussed with a qualified professional. In no way should anything contained in this report be taken as medical advice or form the basis for action without first consulting a qualified medical professional who is familiar with your specific medical situation.