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تسجيل

Myelodysplastic Syndromes: Germline Predisposition – Transformation to Acute Leukemia

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P985

2026-10-18

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Some patients with MDS go undiagnosed until they present with AML. An antecedent unrecognized MDS phase may be suspected on the basis of dysplastic-appearing morphology or long-standing incompletely evaluated cytopenias, but can also be inferred by the presence of MDS-associated mutations, including SF3B1, SRSF2, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2. Absence of these mutations does not imply the converse conclusion that the AML arose de novo; while NPM1 mutations appear to be restricted to de novo AML, mutations in DNMT3A, TET2, and IDH1/2 are not ontogeny-specific. TP53-mutated AML comprises its own category and is associated with prior chemotherapy and complex karyotypes.

In most cases, progression of MDS to AML involves the acquisition of pro-proliferative mutations, which tend to be late, subclonal events. As discussed above, patients who develop secondary AML from an antecedent MDS tend to have a poorer prognosis, with both a lower rate of complete remission and a poorer overall survival, independent of remission, than patients with de novo AML. In unselected populations, some of this difference in outcome can be explained by demographic characteristics associated with secondary AML, including older age and increased number of comorbidities, mirroring the characteristics of the MDS population. However, patients with secondary AML have inferior outcomes even compared to age-matched controls with de novo AML, reflective of the refractory nature of the antecedent MDS. Overcoming the intrinsic resistance to therapy common to most patients with MDS remains one of the central challenges of treating the disease.