Journal of Leukemia
Open Access

Molecular Biomarkers for Relapse Prediction in Acute Lymphoblastic Leukemia

Alexander Scholz^{* *}Correspondence: Alexander Scholz, Department of Oncology, University of Helsinki, Helsinki, Finland, Email:

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Description

Leukemia is a diverse group of hematologic malignancies characterized by the uncontrolled proliferation of abnormal white blood cells in the bone marrow and peripheral blood, continues to pose significant challenges in clinical management due to its heterogeneity, chemoresistance and frequent relapses. Despite advances in chemotherapy, targeted therapies, immunotherapy and hematopoietic stem cell transplantation, the prognosis for leukemia patients remains highly variable. Accurate risk stratification and prognosis assessment are crucial for guiding treatment decisions, optimizing therapy intensity, and improving patient outcomes. Traditional prognostic indicators, such as cytogenetic abnormalities, white blood cell counts at diagnosis, and response to induction therapy, have provided a foundation for patient management. However, they are often insufficient to capture the full complexity of disease biology, leading to variability in treatment outcomes even among patients classified within the same risk category. In this context, novel biomarkers have emerged as promising tools for refining leukemia prognosis, offering the potential to personalize therapy, predict disease progression and monitor minimal residual disease.

Recent research has focused on the identification of molecular and genetic biomarkers that can inform prognosis and guide treatment strategies. Advances in high-throughput sequencing, genomics, transcriptomics, and proteomics have enabled the discovery of numerous candidate biomarkers with prognostic relevance. For instance, in Acute Myeloid Leukemia (AML), mutations in genes such as FLT3, NPM1, CEBPA, IDH1/2, and TP53 have been extensively studied for their impact on patient outcomes. FLT3 Internal Tandem Duplications (ITDs), for example, are associated with high relapse rates and poor overall survival, whereas NPM1 mutations in the absence of FLT3- ITD confer a more favorable prognosis. Integrating these molecular markers with conventional risk factors allows for a more nuanced stratification of patients into favorable, intermediate, and adverse risk categories, guiding the intensity of therapy and suitability for allogeneic stem cell transplantation.

Minimal Residual Disease (MRD) assessment has become an integral part of leukemia prognosis, providing highly sensitive information on disease burden beyond conventional morphological evaluation. The detection of MRD using techniques such as flow cytometry, Quantitative Polymerase Chain Reaction (qPCR), and Next-Generation Sequencing (NGS) has demonstrated strong predictive value for relapse and overall survival across leukemia subtypes. For instance, AML patients achieving MRD negativity after induction therapy have significantly improved relapse-free and overall survival compared to MRD-positive patients. Similarly, MRD monitoring in ALL allows clinicians to identify patients at high risk of relapse and tailor post-remission therapy, including consideration of allogeneic stem cell transplantation or novel targeted therapies. The integration of MRD status with genetic and molecular biomarkers enhances the precision of prognostic assessment and facilitates dynamic treatment adjustments.

Proteomic and metabolomic approaches are increasingly contributing to the identification of novel protein-based biomarkers in leukemia. Dysregulated expression of cell surface markers, signaling proteins, and secreted factors has been correlated with disease aggressiveness and treatment response. For example, overexpression of CD123, CD33 and CD47 on leukemic blasts has been associated with poor prognosis and resistance to chemotherapy. These biomarkers not only provide prognostic information but also serve as therapeutic targets for monoclonal antibodies, antibody-drug conjugates, and immunotherapeutic strategies, illustrating the dual role of biomarkers in prognosis and therapy. Metabolomic profiling has revealed alterations in energy metabolism, amino acid utilization, and redox balance in leukemic cells, offering additional layers of prognostic insight and potential avenues for targeted interventions.