The prognosis for double-hit (DH) multiple myeloma (MM), which has a dire prognosis, is made worse by the inclusion of biallelic inactivation of TP53 in the description of the disease. The 15%–20% of people with MM who had a median overall survival of fewer than 24 months could not be correctly diagnosed by this illness or even by the presence of high-risk cytogenetic abnormalities. 

This sparked the search for other MM patients who could share the same transcriptional traits as those with DH-TP53. For a study, researchers examined RNA-seq, whole-genome, and whole-exome sequencing data from 660 patients with newly diagnosed multiple myeloma (NDMM) from the MMRF (Multiple Myeloma Research Foundation) CoMMpass project to identify the transcriptional signature of TP53 double-hit (DH-TP53) MM. 

In patients with DH-TP53, they discovered 78 genes that were solely dysregulated. Despite not having the biallelic inactivation of TP53, a score based on these genes revealed a group of 50 patients with a similar transcriptional profile (DH-TP53-like group) whose prognosis was extremely poor [median overall survival (OS)< 2 years]. The predictive usefulness of the DH-TP53 score was independently verified using microarray-analyzed gene expression data from 850 NDMM patients. 

Additionally, the standard prognostic categorization of MM patients based on chromosomal abnormalities and the International Staging System (ISS) was improved by the DH-TP53 score.

Reference: onlinelibrary.wiley.com/doi/10.1111/bjh.18410