GENOMIC PROFILING IN HEMATOLOGIC MALIGNANCIES: FROM DIAGNOSIS TO PERSONALIZED THERAPY

Abstract

The clinical management of hematologic malignancies is entering a new era, largely driven by combining next-generation sequencing (NGS) and thorough genomic profiling (CGP). This article discusses the profound impact of these innovations on the practice of medicine in hematologic malignancies, highlighting their transition from research instruments to tools of precision medicine. Presently, integrated DNA and RNA profiling tests show great practicability of patient samples such as peripheral blood, bone marrow, and formalin-fixed paraffin-embedded tissue yielding sufficient material for genomic interrogations. Instead of the old method of focusing on a single gene, integrated CGP covers all types of somatic mutations, like base substitutions, insertions/deletions, copy number alterations, as well as complex gene fusions. From genomes analysis, it comes out that the great majority of patients carry at least one reportable driver mutation, and most of them have potentially targetable mutations which can be addressed by FDA-approved or investigational drugs. Most important recurrent mutations such as TP53 TET2 DNMT3A, FLT3, only guide therapy choices but also serve as a foundation for diagnostic and prognostic evaluation in various histologies that include AML MDS CLL, and lymphoid malignancies