Many multiple myelomas: making more of the molecular mayhem

M Chesi, PL Bergsagel - Hematology 2010, the American …, 2011 - ashpublications.org
Hematology 2010, the American Society of Hematology Education …, 2011ashpublications.org
Multiple myeloma (MM) is malignancy of isotype-switched, BM-localized plasma cells that
frequently results in bone destruction, BM failure, and death. Important molecular subgroups
are identified by three classes of recurrent immunoglobulin gene translocations and
hyperdiploidy, both of which affect disease course. From a clinical standpoint, it is critical to
identify MM patients carrying the t (4; 14) translocation, which is present in 15% of myelomas
and is associated with dysregulation of WHSC1/MMSET and often FGFR3. These patients …
Abstract
Multiple myeloma (MM) is malignancy of isotype-switched, BM-localized plasma cells that frequently results in bone destruction, BM failure, and death. Important molecular subgroups are identified by three classes of recurrent immunoglobulin gene translocations and hyperdiploidy, both of which affect disease course. From a clinical standpoint, it is critical to identify MM patients carrying the t(4;14) translocation, which is present in 15% of myelomas and is associated with dysregulation of WHSC1/MMSET and often FGFR3. These patients should all receive bortezomib as part of their initial induction treatment because this has been shown to significantly prolong survival. In contrast, patients with translocations affecting the MAF family of transcription factors, del17p, or gene-expression profiling (GEP)–defined high-risk disease appear to have a worse prognosis that is not dramatically improved by any intervention. These patients should be enrolled in innovative clinical trials. The remaining patients with cyclin D translocations or hyperdiploidy do well with most therapies, and the goal should be to control disease while minimizing toxicity.
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