New findings in the pathogenesis of two myelodysplastic syndrome subtypes: 5q- syndrome and sideroblastic anaemia, partially relevant for other onco-haematological diseases

Česká verze

Authors: R. Neuwirtová ¹; O. Fuchs ²; A. Jonášová ¹
Authors place of work: I. interní klinika – klinika hematologie, Všeobecná fakultní nemocnice, Lékařská fakulta, Univerzita Karlova Praha ¹; Ústav hematologie a krevní transfuze Praha ²
Published in the journal: Transfuze Hematol. dnes,18, 2012, No. 4, p. 154-161.
Category: Souhrnné práce, původní práce, kazuistiky

Summary

Myelodysplastic syndrome (MDS) is a pre-cancerosis, or rather a pre-leukaemic state. It is not a definitive disease but rather involves heterogeneous clinical manifestations ranging from cytopenias to conditions similar to acute myeloid leukaemia. This characteristic of MDS explains the difficulty of elucidating its pathogenesis. Admirable progress regarding cell structure and metabolism as well as cell growth regulation has extended our understanding of MDS pathogenesis. Recently, two interesting findings in the pathogenesis of 5q -⁠ syndrome and refractory anaemia with ringed sideroblasts (RARS) have been reported. In 5q -⁠ syndrome, ribosomal stress has been identified as the underlying mechanism of refractory anaemia. It has also been partially explained why ribosomal stress does not hamper effective megakaryopoiesis in this MDS subtype. In the majority of RARS patients, a mutation of the SF3B1 gene, which plays a role in pre-mRNA splicing, has been uncovered. The contribution of this SF3B1 mutation to the development of ringed sideroblasts and its role in iron metabolism within erythroblasts represent an impulse for further research. SF3B1 mutation in chronic lymphocytic leukaemia as opposed to RARS is associated with poor prognosis.

Key words:
pathogenesis of MDS, 5q -⁠ syndrome, ribosomal stress, RARS, mutation of SF3B1, defect RNA splicing

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