Early and sensitive detection of PML-A216V mutation by droplet digital PCR in ATO-resistant acute promyelocytic leukemia

Alfonso, Victoria; Iaccarino, Licia; Ottone, Tiziana; Cicconi, Laura; Lavorgna, Serena; Divona, Mariadomenica; Cairoli, Roberto; Cristiano, Antonio; Ciardi, Claudia; Travaglini, Serena; Falconi, Giulia; Hasan, Syed Khizer; Venditti, Adriano; Arcese, William; Voso, Maria Teresa

doi:10.1038/s41375-018-0298-3

Cited by 18 publications

(15 citation statements)

References 6 publications

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“…All five patients who harbored PML mutations showed clinical resistance to ATO‐based therapy, and had progressive disease. In this setting, using a sensitive ddPCR technique we were able to detect the PML ‐A216V at very low copy numbers in patients relapsing after ATO‐ATRA …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…This new insight may be useful for further investigations about the role of FOXO3A in treatment response to ATO in APL patients. In this line, additional studies to identify novel therapeutic agents enabled to restore FOXO3A function may overcome ATO resistance even in patients harboring PML-A216V mutation, accounting for about 30% of ATO-resistant cases [56].…”

Section: Forkhead Box Proteins In Pml/rara (Promyelocytic Leukemiamentioning

confidence: 99%

The Role of Forkhead Box Proteins in Acute Myeloid Leukemia

Gurnari

Falconi

Bellis

et al. 2019

Cancers

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Forkhead box (FOX) proteins are a group of transcriptional factors implicated in different cellular functions such as differentiation, proliferation and senescence. A growing number of studies have focused on the relationship between FOX proteins and cancers, particularly hematological neoplasms such as acute myeloid leukemia (AML). FOX proteins are widely involved in AML biology, including leukemogenesis, relapse and drug sensitivity. Here we explore the role of FOX transcription factors in the major AML entities, according to “The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia”, and in the context of the most recurrent gene mutations identified in this heterogeneous disease. Moreover, we report the new evidences about the role of FOX proteins in drug sensitivity, mechanisms of chemoresistance, and possible targeting for personalized therapies.

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“…They assumed that it may have been present at subclonal level before therapy and then later selected under treatment pressure. These data suggest that ddPCR can be successfully recruited for PML A216V gene mutation screening and that this procedure may allow for the detection of mutant cases earlier than conventional sequencing [46].…”

Section: Dpcr For Detecting Somatic Mutationsmentioning

confidence: 84%

Digital PCR: A Reliable Tool for Analyzing and Monitoring Hematologic Malignancies

Coccaro

Tota

Anelli

et al. 2020

IJMS

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The digital polymerase chain reaction (dPCR) is considered to be the third-generation polymerase chain reaction (PCR), as it yields direct, absolute and precise measures of target sequences. dPCR has proven particularly useful for the accurate detection and quantification of low-abundance nucleic acids, highlighting its advantages in cancer diagnosis and in predicting recurrence and monitoring minimal residual disease, mostly coupled with next generation sequencing. In the last few years, a series of studies have employed dPCR for the analysis of hematologic malignancies. In this review, we will summarize these findings, attempting to focus on the potential future perspectives of the application of this promising technology.

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Early and sensitive detection of PML-A216V mutation by droplet digital PCR in ATO-resistant acute promyelocytic leukemia

Cited by 18 publications

References 6 publications

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

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

The Role of Forkhead Box Proteins in Acute Myeloid Leukemia

Digital PCR: A Reliable Tool for Analyzing and Monitoring Hematologic Malignancies

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