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Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics

Leukemia volume 27, pages 1940–1943 (2013)Cite this article

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Acute erythroid leukemia (AEL) (=AML FAB M6) comprises <5% of adult acute myeloid leukemia (AML), but becomes more frequent with higher age.1 AEL patients were described to have more frequently poor risk cytogenetics and worse survival than other AML subtypes.2 The cytogenetic risk group was suggested to be prognostically relevant for AEL patients, but the diagnosis of AEL was no independent prognostic parameter when the cytogenetic risk group or the history of the disease were considered.3 AEL was described to differ from overall AML, for example, by a lower FLT3 mutation rate.2 It remains unclear whether a diagnosis of AEL per se or the association with poor risk cytogenetic features or other poor risk characteristics causes the more adverse prognosis.3 So far, mutations of FLT3 and NRAS2 only have been studied in more detail in AEL. We previously suggested that the different AML and myelodysplastic syndrome (MDS) subtypes with predominant erythropoiesis may be combined into one category.4 Others proposed that the clinical and genetic features of AML with erythroid predominance are closer to high-grade MDS than to other types of AML.5

We investigated 14 candidate genes combined with the cytogenetic background and the prognostic impact in 92 AEL patients (31 female/61 male; median age, 68.8 years; range: 21.3–88.3 years; Supplementary Table S1). Survival data was available in 74 patients. All patients had erythroleukemia (erythroid/myeloid leukemia),6 pure erythroid leukemia was not considered. Patients received induction and consolidation chemotherapy according to AML Cooperative Group (AMLCG)7 or comparable protocols. Bone marrow samples were sent for diagnosis to the MLL Munich Leukemia Laboratory from August 2005 to May 2012. All patients gave their written consent for genetic analyses and research studies. Part of the patients had been included in a previous study.4 All cases were investigated by cytomorphology, chromosome banding analysis and, in case of a normal karyotype, by array comparative genomic hybridization (CGH). Because of limitations in sample material, we combined data from 454 amplicon deep sequencing (Roche, Branford, CT, USA)8 with Sanger sequencing and melting curve analyses (for details see Supplementary Appendix). The various screening techniques for the different genes are given in Supplementary Table S2. Of note, despite the incongruent molecular screening programme, no significant bias was detectable in terms of detection of minor subclones by deep sequencing in comparison to other assays. Thus, no influence on the subsequent results is expected.

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Author notes

  1. V Grossmann and U Bacher: These authors contributed equally to this work.

Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    V Grossmann, U Bacher, C Haferlach, S Schnittger, F Pötzinger, S Weissmann, A Roller, C Eder, A Fasan, M Zenger, M Staller, W Kern, A Kohlmann & T Haferlach

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  1. V Grossmann
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  2. U Bacher
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Correspondence to T Haferlach.

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Competing interests

VG, UB, FP, SW, AR, CE, AF, MZ, MS, and AK are employed by the MLL Munich Leukemia Laboratory GmbH. CH, SS, WK and TH are part owners of the MLL Munich Leukemia Laboratory GmbH.

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Author contributions

VG, CH, AK and TH performed study design. UB and VG performed data analysis and wrote the first manuscript draft. UB and TH performed cytomorphology. VG, SS, FP, SW, CE, AF, and AK performed molecular analyses. AR was responsible for bioinformatics. CH, MZ, and MS did cytogenetic analyses. WK contributed to statistical analysis. All authors contributed to writing of the manuscript, reviewed the final version, and gave consent to the final version.

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Grossmann, V., Bacher, U., Haferlach, C. et al. Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics. Leukemia 27, 1940–1943 (2013). https://doi.org/10.1038/leu.2013.144

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