Multiple Myeloma IGH Reflex

IGH rearrangements are disease-initiating events in up to 40% of multiple myeloma (MM) cases, as well as the MM precursor, monoclonal gammopathy of undetermined significance (MGUS).¹ These rearrangements result in fusions with several recurrent partner genes. The cryptic IGH/MAF fusion subjects MAF to IGH’s powerful enhancer, resulting in MAF upregulation in plasma cells. The abnormality occurs in 5% of MM and 1-5% of MGUS patients. It’s considered an early stage biomarker for the disease. IGH/MAFB fusion is found in about 1% of MM. Consistent with other IGH/MAF family fusions, it’s considered a high-risk MM marker.3 The fusion upregulates MAFB expression, which promotes transformation of fibroblasts and enhances tumor cell proliferation.4 CCND1 is found fused to IGH in 15-20% of MM patients, representing the most frequent rearrangement in the disease.3 The fusion is usually balanced, and occurrs alongside monosomy 13 in about 25% of cases. It’s considered a standard risk alteration in MM. IGH/FGFR3 fusion occurs in 15–20% of MM patients.5 The percentage of plasma cells harboring IGH/FGFR3 increases significantly with disease progression, evidence that the alteration drives MM development.5