Hematopoiesis Klonal sebagai Prediktor Risiko Transformasi Leukemia dan Potensinya sebagai Target Precision Medicine: Sebuah Tinjauan Literatur

Abstract

Clonal hematopoiesis (CH) is characterized by the expansion of hematopoietic cell clones carrying somatic genetic alterations in the absence of diagnostic criteria for a hematologic neoplasm. Although most individuals with CH do not progress to malignancy, certain molecular and clinical features may increase the risk of developing myeloid neoplasms, including acute myeloid leukemia (AML). Understanding the factors that influence clonal expansion and evolution is essential for improving risk stratification and advancing precision medicine approaches.This review aimed to analyze the association between the molecular and clinical characteristics of CH and the risk of progression to myeloid neoplasms, identify potential factors for risk stratification, and evaluate their implications for biomarker development and precision medicine. A literature review was conducted of scientific publications addressing CH, clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of undetermined significance (CCUS), somatic genetic mutations, clonal dynamics, progression to myeloid neoplasms, biomarkers, and precision medicine approaches. The analysis focused on mutation types and combinations, clone size and variant allele frequency (VAF), the dynamics of clonal expansion, the presence of cytopenia, clinical factors, and alterations in the hematopoietic microenvironment that may influence disease evolution. Available evidence indicates that the risk of CH progression is heterogeneous and cannot be determined solely by the presence of a single mutation. Mutations in DNMT3A, TET2, and ASXL1 are frequently detected, but their prognostic implications vary. The risk of progression tends to increase in individuals with larger clones, higher VAF or progressive clonal expansion over time, high-risk or multiple mutations, and concomitant cytopenia or features consistent with CCUS. Interactions among intrinsic alterations in hematopoietic cells, inflammation, and the hematopoietic microenvironment may also contribute to clonal selection and expansion. Integrating molecular profiles with clinical characteristics may provide more informative risk stratification than the use of hematological parameters alone. Nevertheless, evidence regarding interventions that directly target CH to prevent leukemic transformation remains limited. CH represents a preneoplastic clonal state that may progress to myeloid neoplasms in a subset of individuals. Mutation type, combinations of genetic alterations, clone size and dynamics, cytopenia, and microenvironmental factors should be considered when assessing the risk of progression. Integration of molecular and clinical data may support individualized monitoring and the development of precision medicine strategies. However, longitudinal and prospective studies are needed to validate biomarkers with consistent predictive value and to identify safe and effective interventions for preventing transformation to leukemia.

Keywords: Acute Myeloid Leukemia, Clonal Hematopoiesis, Clonal Evolution, Somatic  Mutations,  Precision Medicine, Risk Stratification