Molecular diagnostics inhabit an increasingly central role in characterizing hematopoietic malignancies. This brief review summarizes the genomic targets important for many major categories of hematopoietic neoplasia by focusing on disease pathogenesis. In myeloid disease, recurrent mutations in key functional classes drive clonal hematopoiesis, on which additional variants can specify clinical presentation and accelerate progression. Lymphoblastic leukemias are frequently initiated by oncogenic fusions that block lymphoid maturation while, in concert with additional mutations, driving proliferation. The links between genetic aberrations and lymphoma patient outcomes have been clarified substantially through the clustering of genomic profiles. Finally, the addition of next-generation sequencing strategies to cytogenetics is refining risk stratification for plasma cell myeloma. In all categories, molecular diagnostics shed light on the unique mechanistic underpinnings of each individual malignancy, thereby empowering more rational, personalized care for these patients.
Molecular diagnostics play a central role in the evaluation of hematopoietic malignancies.
The molecular profiles of myeloid, lymphoid, and plasmacytic neoplasms can provide key diagnostic, prognostic, and therapeutic information while elucidating underlying biology.
Next-generation sequencing technologies have empowered more personalized tumor characterization and individualized therapy.
Once relegated to investigational or ancillary roles, nucleic acid-based molecular tests have become essential for the diagnosis and management of most hematologic malignancies. Molecular assays can offer improved analytical sensitivity, wide and customizable target breadth, and operational scalability/automation. However, their greatest strength lies in the ability to directly illuminate genetic alterations that drive disease pathogenesis. These insights allow diagnosticians to use a powerful, personalized approach to disease characterization, predict future disease behavior, and provide targets for therapy in some cases.
Recognizing these advances, the World Health Organization (WHO) and other organizations continue to expand the number of molecular alterations used as primary diagnostic criteria in their classifications of hematopoietic tumors.
Meanwhile, a pipeline of new molecular technologies continually narrows the gap between mechanistic insights and their application to patient care. In other words, the days of molecular diagnostics in an auxiliary role are behind us.
This review aims to provide a concise overview of the genetic alterations most important to detect in several major categories of adult hematopoietic neoplasia. For myeloid neoplasms, lymphoblastic leukemia/lymphoma, a selection of B and T cell lymphomas, and plasma cell neoplasms, we will focus on aberrations with diagnostic or prognostic importance and outline key techniques used for their detection. Although not a comprehensive review, this discussion should offer a guideline for building a minimal panel of genetic targets in the routine evaluation of these disease categories and provide a logical testing framework based on their pathogenic mechanisms.