

![]() |
Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia |
|
Authors | ![]() | |
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 | Adolescent — Adult — Aged — Aged, 80 and over — Alleles — Biomarkers, Tumor — Chromosome Aberrations — Clonal Evolution/genetics — Female — High-Throughput Nucleotide Sequencing — Humans — In Situ Hybridization — Fluorescence — Leukemia, Myeloid, Acute/diagnosis/genetics/mortality — Male — Middle Aged — Mutation — Neoplasm, Residual/diagnosis/genetics — Precision Medicine — Prognosis — Young Adult | |
Identifiers | PMID: 28302711 | |
Full text | ||
Research group | Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982) | |
Citation (ISO format) | 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 https://archive-ouverte.unige.ch/unige:144215 |