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Diagnosis and Prognosis: Molecular

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Book cover Myelodysplastic Syndromes

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

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Abstract

Cytogenetic abnormalities seen in 50% of patients by conventional banding techniques have always aided in diagnosis and prognostication in primary MDS. The subsequent advent of molecular karyotyping techniques such as SNP array karyotyping has improved the resolution, enabled detection of cryptic microdeletions and copy-neutral loss of heterozygosity and also facilitated the discovery of pathognomonic genes localised to regions of deletion or UPD. The availability of cost-effective high-throughput sequencing technologies has unravelled our understanding of the aberrant mechanisms underlying the pathogenesis of MDS. The plethora of acquired genomic abnormalities in 80–90% of patients, some relatively unique to MDS such as epigenetic and spliceosome mutations, has an impact on diagnosis, prognosis, risk stratification and choice of treatment. The well-established diagnostic and prognostic systems are incorporating the additional genomic data leading to ongoing refinements of WHO classification system and IPSS-R prognostic groups. Dysplasia in >10% of either one or more cell lineages still remains MDS defining, although it is subject to interobserver variability and lack of reproducibility even among expert haematopathologists. As many of the most common MDS-associated somatic mutations (DNMT3A, TET2, ASXL1) are found in the blood of healthy individuals without cytopenia or dysplasia, termed as clonal haematopoiesis of indeterminate potential (CHIP), and are not specific for MDS, somatic mutations are currently excluded as a diagnostic criteria for MDS.

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Authors and Affiliations

  1. Department of Haematological Medicine, King’s College Hospital NHS Foundation Trust, London, UK

    Austin G. Kulasekararaj & Ghulam J. Mufti

  2. King’s College London, London, UK

    Austin G. Kulasekararaj & Ghulam J. Mufti

  3. Inserm, Paris, France

    Olivier Kosmider

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  1. Austin G. Kulasekararaj
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  2. Olivier Kosmider
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  3. Ghulam J. Mufti
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Correspondence to Austin G. Kulasekararaj .

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  1. Medizinische Klinik und Poliklinik 1, Universitätsklinikum Dresden Medizinische Klinik und Poliklinik 1, Dresden, Sachsen, Germany

    Uwe Platzbecker

  2. Department of Hematology, Hospital Saint Louis, Paris, France

    Pierre Fenaux

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Kulasekararaj, A.G., Kosmider, O., Mufti, G.J. (2018). Diagnosis and Prognosis: Molecular. In: Platzbecker, U., Fenaux, P. (eds) Myelodysplastic Syndromes . Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-319-76879-3_2

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