Therapy-related myeloid neoplasms

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Therapy-related myeloid neoplasms (t-MNs), including therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML), share similar pathogenesis and poor prognosis.
• Recent genetic characterization has significantly advanced the understanding of t-MNs.
• The WHO classification now combines t-MDS and t-AML into a single entity, t-MNs.

Purpose of the Study:

• To review the current understanding of the pathogenesis of therapy-related myeloid neoplasms.
• To highlight the diagnostic and prognostic impact of recurrent mutations in t-MNs.
• To discuss the implications of genetic profiling and minimal residual disease assessment in guiding treatment decisions.

Main Methods:

• Review of recent genetic characterization studies and sequencing data in t-MN patients.
• Analysis of molecular aberrations, including TP53 mutations and fusion genes.
• Examination of treatment strategies based on genetic risk profiles.

Main Results:

• TP53 mutations are the most frequent molecular aberration in t-MNs (33%), often arising from pre-existing resistant clones.
• Fifteen percent of t-AML patients have favorable risk fusion genes, while 50% exhibit adverse cytogenetics.
• High nonrelapse mortality is observed in t-MN patients post-allogeneic hematopoietic cell transplantation due to treatment-induced vulnerabilities.

Conclusions:

• Genetic risk stratification is crucial for guiding treatment decisions in t-MNs.
• Assessment of minimal residual disease aids in optimizing allogeneic transplantation for favorable-risk patients.
• Understanding the molecular pathogenesis, particularly TP53 mutations, is key to improving outcomes for t-MN patients.