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Stem cell transplantation

High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS)

Leukemia volume 29, pages 1928–1938 (2015)Cite this article

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Abstract

Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1–1.9)) than in PB (CN:1.5 (1–1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1–96%)) compared with BM (median 29% (1–100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows.

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Acknowledgements

We acknowledge Leukaemia Lymphoma Research (UK) and King's College London for funding the King's College Haemato-Oncology Tissue Bank, from which all local samples were processed.

Author Contributions

GJM conceived the study. AMM, JG, FM, AES, TG, SB and SM performed experiments. AMM, AGK, MA, GJM and JG contributed to design, analysis and manuscript preparation. RI, AGK and GJM provided clinical details and analysis.

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  1. A M Mohamedali and J Gäken: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Haematological Medicine, The Rayne Institute, King’s College London School of Medicine, London, UK

    A M Mohamedali, J Gäken, M Ahmed, F Malik, A E Smith, S Best, S Mian, T Gaymes, A G Kulasekararaj & G J Mufti

  2. Department of Haematology, Department of Haematology, King’s College Hospital, London, UK

    A M Mohamedali, M Ahmed, A E Smith, S Best, T Gaymes, R Ireland, A G Kulasekararaj & G J Mufti

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Correspondence to G J Mufti.

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Mohamedali, A., Gäken, J., Ahmed, M. et al. High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS). Leukemia 29, 1928–1938 (2015). https://doi.org/10.1038/leu.2015.110

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