How to Read a Next-Generation Sequencing Report for AML and MDS? What Hematologists Need to Know

Area of Science:

• Hematology
• Genomics
• Oncology

Background:

• Acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are significant hematologic malignancies.
• Next-generation sequencing (NGS) has revolutionized the molecular characterization of these diseases.

Purpose of the Study:

• To review the advantages, limitations, and future of NGS in AML and MDS clinical management.
• To emphasize the biological and technical principles of NGS in these hematologic malignancies.
• To guide clinicians in interpreting complex molecular data for diagnosis, prognosis, and therapy.

Main Methods:

• Targeted NGS panels are the current standard for detecting recurrent mutations, structural variants, and gene fusions.
• Whole-genome, whole-exome, and RNA sequencing offer broader detection but are less practical for routine diagnostics.
• Bioinformatic pipelines and quality metrics are essential for accurate variant calling and validation.

Main Results:

• NGS is integrated into diagnostic frameworks (WHO 2022, ICC) and prognostic models (ELN-2022, IPSS-M).
• NGS enables measurable residual disease (MRD) monitoring, with increasing clinical utility.
• Diagnostic NGS identifies germline predisposition syndromes, impacting treatment and transplantation.

Conclusions:

• NGS significantly influences diagnosis, risk stratification, and therapeutic decision-making in AML and MDS.
• Standardization of NGS-based MRD monitoring is ongoing.
• Understanding NGS fundamentals is vital for clinicians managing these complex hematologic malignancies.