Molecular genetic profile and immunophenotyping of autologous hematopoietic stem cells in multiple myeloma: application of NGS method and monitoring of minimal residual disease
Mygal I.I., Khudziy S.S., Savuliak G.R., Shmygelska S.M., Tsyapka O.M., Maslyak Z.V.
Summary. Introduction. Multiple myeloma (MM) is a malignant plasma cell neoplasm that remains incurable, although the introduction of new drugs and high-dose chemotherapy (HDT) with autologous hematopoietic stem cell transplantation (auto-HSCT) has significantly improved patient survival. However, relapse eventually develops in almost all patients, which necessitates an in-depth assessment of residual disease and individualized therapy. Aim. To summarize current data on the molecular genetic abnormalities and immunophenotypic characteristics of myeloma cells, their impact on treatment selection and prognosis in MM, as well as on the role of next-generation sequencing (NGS) in detecting minimal residual disease (MRD) after therapy, with an emphasis on personalized medicine. Main points of the review. MM is characterized by a complex genetic profile: recurrent chromosomal translocations, gene copy number alterations, and point mutations are present. Among the most frequent molecular abnormalities are mutations in RAS family genes (KRAS, NRAS) and other genes (TP53, DIS3, FAM46C, BRAF, etc.), as well as cytogenetic anomalies (17p deletion, translocations t(4;14), t(11;14), etc.), which influence the disease course. Immunophenotypically, tumor plasma cells differ from normal ones: they express CD38 and CD138 but usually lack CD19, and often show CD56 or other aberrant markers (e.g., CD117 or lack of CD27). Sensitive methods for MRD detection — multicolor flow cytometry (NGF) and NGS-based molecular techniques — are used to assess the depth of response to treatment. The absence of clonal plasma cells at a level of <10–5 (MRD negativity) is associated with significantly longer relapse-free and overall survival. The NGS method (e.g., the clonoSEQ technology) can detect single tumor cells among ~1,000,000 normal cells and was approved by the Food and Drug Administration (FDA) as a standardized approach for MRD monitoring in MM. NGS analysis identifies a unique tumor immunoglobulin gene “clonotype” in each patient and quantitatively tracks it in the bone marrow or even peripheral blood after treatment. Conclusions. The integration of molecular genetic profiling and immunophenotyping of myeloma into clinical practice allows for risk stratification and personalized therapy. MRD monitoring using highly sensitive methods (NGS / NGF) is becoming a new standard for assessing MM treatment efficacy, enabling timely decisions regarding therapy intensity (e.g., duration of maintenance therapy) and identification of patients at high risk of early relapse for treatment strategy adjustment. The implementation of these methods in Ukraine is a promising step toward improving MM treatment outcomes.
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