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; Marzac, Christophe; Fava, Fanny; Mamez, Anne-Claire; Lapusan, Simona; Isnard, Françoise; Mohty, Mohamad; Legrand, Ollivier; Douay, Luc; Bilhou-Nabera, Chrystele; Delhommeau, François

doi:10.3324/haematol.2016.159681

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Title		Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia
Authors		Hirsch, Pierre Tang, Ruoping Abermil, Nassera Flandrin, Pascale Moatti, Hannah Favale, Fabrizia Suner, Ludovic Lorre, Florence Marzac, Christophe Fava, Fanny Mamez, Anne-Claire Lapusan, Simona Isnard, Françoise Mohty, Mohamad Legrand, Ollivier Douay, Luc Bilhou-Nabera, Chrystele Delhommeau, François show all authors [1 - 18]
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		DOI: 10.3324/haematol.2016.159681 PMID: 28302711
Full text		Article (Published version) (3.4 MB) - Free access
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