2 – Changes in gene expression
Several reports on gene expression in MM have been published. Using non-supervised analyses, three reports identified subgroups mostly driven by chromosomal aberrations [17–19]. The first report identified eight different subgroups, mainly based on cyclin D gene expression and on the different 14q32 recurrent translocations. This molecular classification was refined in 2006, identifying seven subclasses of myeloma . A first class is defined by the translocation t(4;14), identified by overexpression of the MMSET and/or FGFR3 genes. The second class is defined by upregulation of one of the MAF genes, related to the translocations t(14;16) or t(14;20).
Cases with CCND1 or CCND3 upregulation (due to the translocations t(11;14) or t(6;14)) clustered in two different groups, which were named CD1 and CD2. The CD2 group was characterized by CD20 expression. The fifth class was characterized by hyperdiploidy. The sixth and seventh classes were characterized by a low incidence of bone disease, according to a low Dickkopf 1 (DKK1) expression, whereas the last class was characterized by high expression of genes involved in proliferation. This molecular classification has been partially confirmed by Broyl et al . The ‘low bone disease’ class was not confirmed. By contrast, three other classes were identified: one class enriched by ‘myeloid’ genes (that could be related to plasma cell sorting problems), one class characterized by overexpression of cancer testis antigen genes, and finally a class defined by overexpression of positive regulators of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Whether these subclasses define true MM subentities has not yet been demonstrated.
All topics within this chapter
1. Chromosomal aberrations
2. Changes in gene expression
3. Bone marrow microenvironment and cytokine network