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Acute myeloid Leukemia

Minimal residual disease (MRD) monitoring and mutational landscape in AML with RUNX1-RUNX1T1: a study on 134 patients

Leukemia volume 32, pages 2270–2274 (2018)Cite this article

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The cure rate in AML depends on patient’s age and performance status, cytogenetics, early blast clearance and sustainable first complete remission. Investigation of minimal residual disease (MRD) is possible by multiparameter-flow cytometry or molecular techniques. Recent findings have further depicted a broad spectrum of molecular markers in AML in 99% of patients [1]. This broadens the set of targets for MRD assessment and will hopefully help to better individualize treatment strategies. MRD monitoring by qPCR is feasible in AML with RUNX1-RUNX1T1 fusion. The absence of RUNX1-RUNX1T1 transcripts is considered as complete molecular remission (CMR). Risk stratification according to MRD is possible and initial studies allocating MRD positive patients to allogeneic stem cell transplantation have been undertaken [2]. However, despite CMR about 10–30% of patients relapse [3, 4].

This analysis aims to understand the clinical use of PCR based MRD monitoring in AML with RUNX1-RUNX1T1 fusion outside clinical trials. We specifically address chosen time points for measurements, choice of peripheral blood (PB) vs bone marrow (BM) as sample material for follow-up testing and evaluate the value of CMR as an absolute MRD negativity. In addition, we performed 63 gene panel sequencing to analyze recurrent mutations and their association to CMR and outcome.

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Acknowledgements

We thank all patients and clinicians for their participation in this study and all co-workers in our laboratory for their excellent technical assistance.

Author contributions

AH and TH designed the study. AH interpreted the data and wrote the manuscript. SJ, MM AF and NN did molecular analyses. TH was responsible for cytomorphologic analyses, CH for cytogenetic and FISH analyses and WK for immunophenotyping. All authors read and contributed to the final version of the manuscript.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    Alexander Höllein, Sabine Jeromin, Manja Meggendorfer, Annette Fasan, Niroshan Nadarajah, Wolfgang Kern, Claudia Haferlach & Torsten Haferlach

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  1. Alexander Höllein
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  2. Sabine Jeromin
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Correspondence to Torsten Haferlach.

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AH, SJ, MM, AF, NN: Employment by MLL Munich Leukemia Laboratory; CH, WK, TH: Equity ownership of MLL Munich Leukemia Laboratory. CH, WK, and TH are part owners of the MLL Munich Leukemia Laboratory. AH, SJ, MM, AF and NN are employed by the MLL Munich Leukemia Laboratory.

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Höllein, A., Jeromin, S., Meggendorfer, M. et al. Minimal residual disease (MRD) monitoring and mutational landscape in AML with RUNX1-RUNX1T1: a study on 134 patients. Leukemia 32, 2270–2274 (2018). https://doi.org/10.1038/s41375-018-0086-0

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