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Molecular characterization of acute erythroid leukemia (M6-AML) using targeted next-generation sequencing

Leukemia volume 30, pages 966–970 (2016)Cite this article

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Acute erythroid leukemia (AEL) is a morphologically distinct, infrequent (<5%) acute myeloid leukemia (AML) designed as M6 in the French–American–British (FAB) classification.1 The World Health Organization classification recognizes two subclasses, M6a, a leukemia with myeloid blast cells, and M6b, a very rare, purely erythroid AML.2 It may be difficult to distinguish between a myelodysplastic syndrome and AEL because of the erythroblastic proliferation, which is increased when dysplasia is present.3 No recurrent cytogenetic abnormality is specific of AEL and the prognosis is poor with a median survival of 17 months.4 A study of 14 genes in a series of 92 cases has shown that mutations are frequent in AEL and somewhat differ from the other AMLs by the lower and higher proportion of FLT3-ITD and TP53 mutations, respectively.5 Only three cases of AEL are reported in the TCGA database.6 To further characterize AEL, determine whether it constitutes a distinct class of AML and document the reasons for its poor prognosis, we searched for molecular alterations in 40 M6a-AMLs using array comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) of 106 genes known or suspected to have a role in myeloid malignancies or in erythrocyte differentiation.

Blood or bone marrow samples were collected at diagnosis between 1990 and 2014. These samples and their associated data were obtained from the IPC/CRCM Tumor Bank, that operates underauthorization #AC-2007-33 granted by the French Ministry of Research. Written consents of patients were obtained, according to our ethical committee regulations and Biobank procedures. Median age at diagnosis was 60 years. Karyotype was normal in 16 cases out of 38 (2 were unavailable) and complex in 13. Recurrent abnormalities were loss of chromosome arms 5q, 7q and 20q. Prognosis assessment based on karyotype was intermediate in 24 cases and unfavorable in 14. According to the European Leukemia Net (ELN) classification, 5 patients were classified as favorable, 11 as intermediate I, 8 as intermediate II and 14 as adverse (Supplementary Table S1). DNA extraction was carried out as described previously.7 For each sample, a library of all coding exons and intron–exon boundaries of the 106 genes (listed in Supplementary Table S2) was constructed with the HaloPlex target enrichment system (Agilent Technologies, Santa Clara, CA, USA), designed as ‘hemato V10’ (Design ID: 27066-1412699001), and sequencing was carried out using an Illumina MiSeq apparatus (San Diego, CA, USA).8 For aCGH, we used high-resolution 4 × 180 K CGH microarrays (SurePrint G3 Human CGH Microarray Kit; Agilent Technologies, Massy, France).9

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Acknowledgements

Our work is supported by Inserm, the Paoli-Calmettes Institute and an SIRIC grant (INCa-DGOS-Inserm 6038, specific grant to VGB).

Author contributions

VGB and DB were the principal investigators for this study. VGB, AM, MJM and NV recruited the patients, and collected the samples and the biological annotations. NCe, NCa, SG and JA did the laboratory work, whereas AG did the bioinformatics analyses and MJM the cytogenetic analyses. MC supervised the aCGH and NGS experiments and the analyses. VGB, NCe and DB wrote the paper.

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Authors and Affiliations

  1. Laboratoire d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR1068 Inserm, Institut Paoli-Calmettes, CNRS UMR725, Marseille, France

    N Cervera, N Carbuccia, S Garnier, A Guille, J Adélaïde, A Murati, M-J Mozziconacci, M Chaffanet, D Birnbaum & V Gelsi-Boyer

  2. Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France

    A Murati, M-J Mozziconacci & V Gelsi-Boyer

  3. Aix-Marseille Université, Marseille, France

    N Vey, M Chaffanet, D Birnbaum & V Gelsi-Boyer

  4. Département d’Hématologie, Institut Paoli-Calmettes, Marseille, France

    N Vey

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  1. N Cervera
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Correspondence to V Gelsi-Boyer.

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Cervera, N., Carbuccia, N., Garnier, S. et al. Molecular characterization of acute erythroid leukemia (M6-AML) using targeted next-generation sequencing. Leukemia 30, 966–970 (2016). https://doi.org/10.1038/leu.2015.198

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