Update on cytogenetic and molecular changes in myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and a high propensity to transform to acute myeloid leukemia (AML). In the pathogenesis of the disease, both gene mutations and cytogenetic changes play an important role. The latter have been integrated into prognostic scoring systems including the IPSS (International Prognostic Scoring System) and WPSS (World Health Organization [WHO] classification-based Prognostic Scoring System). In these systems and in multivariate analyses comparing clinical and genetic data, complex karyotypes are associated with a particularly poor prognosis. del(5q) plays a distinct role by classifying the only genetically defined WHO subtype. Also, due to advancement in technology such as whole genome sequencing, the number of known mutations occurring in MDS is steadily increasing. Important recent discoveries include mutations in EZH2, DNMT3A, ASXL1 and IDH1/2. Like TET2, the most commonly mutated gene in MDS, all are involved in epigenetic regulation. Mutations such as ASXL1, RUNX1, EZH2, ETV6/TEL and TP53 have an adverse impact on patient overall survival. Early evidence suggests that some mutations might influence treatment response, necessitating reassessment of the prognostic effect of genetic alterations in the light of every new treatment. This review discusses clinical and biological effects of the most common cytogenetic and molecular aberrations in patients with MDS.

Keywords::

• Myelodysplastic syndrome
• cytogenetics
• deletion 5q
• complex karyotype
• prognostic marker
• molecular marker

Acknowledgements

We are grateful for financial support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) for the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), grant No. DJCLS R 10/22 from the Deutsche-José-Carreras Leukämie-Stiftung e.V.; grant No. 109003 from the Deutsche Krebshilfe e.V; and grant No. M 47.1 from the H. W. & J. Hector Stiftung.

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