TY - JOUR
T1 - Mutational landscape of patients with acute promyelocytic leukemia at diagnosis and relapse
AU - Iaccarino, Licia
AU - Ottone, Tiziana
AU - Alfonso, Valentina
AU - Cicconi, Laura
AU - Divona, Mariadomenica
AU - Lavorgna, Serena
AU - Travaglini, Serena
AU - Ferrantini, Aleandra
AU - Falconi, Giulia
AU - Baer, Constance
AU - Usai, Monica
AU - Forghieri, Fabio
AU - Venditti, Adriano
AU - Del Principe, Maria Ilaria
AU - Arcese, William
AU - Voso, Maria Teresa
AU - Haferlach, Torsten
AU - Lo-Coco, Francesco
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.25573
DO - 10.1002/ajh.25573
M3 - Article
C2 - 31292998
AN - SCOPUS:85069930843
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
ER -