Mutational landscape of patients with acute promyelocytic leukemia at diagnosis and relapse

Licia Iaccarino, Tiziana Ottone, Valentina Alfonso, Laura Cicconi, Mariadomenica Divona, Serena Lavorgna, Serena Travaglini, Aleandra Ferrantini, Giulia Falconi, Constance Baer, Monica Usai, Fabio Forghieri, Adriano Venditti, Maria Ilaria Del Principe, William Arcese, Maria Teresa Voso, Torsten Haferlach, Francesco Lo-Coco

Research output: Contribution to journalArticlepeer-review


Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P =.009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P =.0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P <.0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile.

Original languageEnglish
JournalAmerican Journal of Hematology
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Hematology


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