February 28, 2025
Hematopoietic and lymphocytic neoplasms (HLNs) are a diverse group of malignancies affecting blood and lymphatic systems, with outcomes varying from manageable conditions to fatal diseases. Traditional classifications rely on morphology, karyotyping, and fluorescence in situ hybridization (FISH). However, recent advancements in next-generation sequencing (NGS) allow simultaneous genetic profiling of multiple genes, enhancing diagnostic precision and therapeutic strategies. This review examines key molecular applications in diagnosing and managing HLNs, addressing current challenges and proposing solutions to optimize clinical utility.
Chronic Myeloid Leukemia (CML)
CML, historically identified by leukocytosis, is characterized by the BCR::ABL1 fusion gene resulting from the Philadelphia chromosome translocation. This oncogenic fusion drives aberrant tyrosine kinase activity, promoting unchecked proliferation. The introduction of imatinib, a targeted tyrosine kinase inhibitor (TKI), revolutionized CML treatment, leading to normalized white blood cell (WBC) counts within months. However, resistance mutations necessitate molecular monitoring via quantitative PCR, FISH, and karyotyping, ensuring optimal therapeutic adjustments.
Molecular Applications in BCR::ABL1-Negative Myeloid Neoplasms
Certain myeloid neoplasms, such as chronic neutrophilic leukemia (CNL) and chronic eosinophilic leukemia (CEL), lack the BCR::ABL1 fusion gene but exhibit distinct genetic markers like CSF3R mutations in CNL. Classical myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, driven by JAK2, MPL, or CALR mutations. The application of NGS enables comprehensive mutational profiling, aiding accurate diagnosis and prognostication.