TO THE EDITOR:

Recently, biallelic (“double hit”) TP53 inactivation, occurring in 2% to 4% of newly diagnosed multiple myeloma (MM) patients, was identified as an ultimate high-risk feature of MM, being associated with median survival of <2 years.1-3  We and others have shown that the incidence of TP53 mutations4-6  and deletion of the arm p13 of chromosome 17 (del17p) increases with the progression of the disease. The implications of monoallelic TP53 lesions for the clinical outcome remain controversial,1,8,9  but clonal selection and evolution is a common feature of myeloma progression,10-15  and patients with TP53 wild-type (WT) or monoallelic inactivation may present a double hit on relapse. Here, we addressed the hypothesis that sequential acquisition of TP53 hits lead to a gain of proliferative fitness of MM cancer cells, inducing the expansion and domination of the affected...

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