Molecular Basis of Disease Progression in Multiple Myeloma

23 Jun 2022 16:30 17:00
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Molecular basis of disease progression in myeloma

 

Azlan Husin

School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia

 

Multiple myeloma is the top 5 common haematologic malignancies; it is a genetically complex disease with heterogenous in clinical course and yet incurable in most patients affected. It represents classical example of multi-hit carcinogenesis as their key common initial genetic alterations were also frequently found in its predecessor ie MGUS and smouldering myeloma. Common initial genetic abnormalities like hyperdiploidy and recurrent IgH mutation are then followed by novel mutations (second mutational hit) like KRAS, BRAF, del17p: TP53 etc as the disease progresses and shaping downstream phenotype and prognosis. Some of these mutations are driver mutations whereas the others are just passenger mutations. It is also well accepted the phenomenon of clonal or subclonal tides that explain clonal selection and evolution after exposure to certain drugs. Optimal understanding of these evolution and especially so driver and/or actionable mutations is important to properly utilise appropriate tools for diagnosis, prognostication and perhaps further refine therapeutic strategy. Advances in the detection of chromosomal aberrations via fluorescence in situ hybridization, mutational analysis using next-generation sequencing, epigenetic profiling, and investigations into the bone marrow microenvironment have added to the understanding of this family of hematologic malignancies. Close collaboration between treating clinicians and laboratory scientists is essential to better manage our patients with cutting edge technology and perhaps strategizing research projects that will benefit future patients