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Diagnosis and Prognosis: Molecular

  • Austin G. Kulasekararaj
  • Olivier Kosmider
  • Ghulam J. Mufti
Chapter
Part of the Hematologic Malignancies book series (HEMATOLOGIC)

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.

Keywords

Myelodysplastic syndromes IPSS score Cytogenetic risk group Gene mutations Epigenetic and splicing SF3B1 and TP53 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Austin G. Kulasekararaj
    • 1
    • 2
  • Olivier Kosmider
    • 3
  • Ghulam J. Mufti
    • 1
    • 2
  1. 1.Department of Haematological MedicineKing’s College Hospital NHS Foundation TrustLondonUK
  2. 2.King’s College LondonLondonUK
  3. 3.InsermParisFrance

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