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Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia

Hirsch, Pierre
Tang, Ruoping
Abermil, Nassera
Flandrin, Pascale
Moatti, Hannah
Favale, Fabrizia
Suner, Ludovic
Lorre, Florence
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Published in Haematologica. 2017, vol. 102, no. 7, p. 1227-1237
Abstract The genetic landscape of adult acute myeloid leukemias (AML) has been recently unraveled. However, due to their genetic heterogeneity, only a handful of markers are currently used for the evaluation of minimal residual disease (MRD). Recent studies using multi-target strategies indicate that detection of residual mutations in less than 5% of cells in complete remission is associated with a better survival. Here, in a series of 69 AMLs with known clonal architecture, we design a clone-specific strategy based on fluorescent in situ hybridization and high-sensitivity next generation sequencing to detect chromosomal aberrations and mutations, respectively, in follow-up samples. The combination of these techniques allows tracking chromosomal and genomic lesions down to 0.5-0.4% of the cell population in remission samples. By testing all lesions in follow-up samples from 65 of 69 evaluable patients, we find that initiating events often persist and appear to be, on their own, inappropriate markers to predict short-term relapse. In contrast, the persistence of two or more lesions in more than 0.4% of the cells from remission samples is strongly associated with lower leukemia-free and overall survivals in univariate and multivariate analyses. Although larger prospective studies are needed to extend these results, our data show that a personalized, clone-specific, MRD follow up strategy is feasible in the vast majority of AML cases.
Keywords AdolescentAdultAgedAged, 80 and overAllelesBiomarkers, TumorChromosome AberrationsClonal Evolution/geneticsFemaleHigh-Throughput Nucleotide SequencingHumansIn Situ HybridizationFluorescenceLeukemia, Myeloid, Acute/diagnosis/genetics/mortalityMaleMiddle AgedMutationNeoplasm, Residual/diagnosis/geneticsPrecision MedicinePrognosisYoung Adult
PMID: 28302711
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Research group Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982)
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HIRSCH, Pierre et al. Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia. In: Haematologica, 2017, vol. 102, n° 7, p. 1227-1237. doi: 10.3324/haematol.2016.159681

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Deposited on : 2020-11-05

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