Drug Resistance Biomarkers and Their Clinical Applications in Childhood Acute Lymphoblastic Leukemia

Abstract

Biomarkers are biological molecules found in body fluids or tissues, which can be considered as indications of a normal or abnormal process, or of a condition or disease. There are various types of biomarkers based on their application and molecular alterations. Treatment-sensitivity or drug resistance biomarkers include prognostic and predictive molecules with utmost importance in selecting appropriate treatment protocols and improving survival rates. Acute lymphoblastic leukemia (ALL) is the most prevalent hematological malignancy diagnosed in children with nearly 80% cure rate. Despite the favorable survival rates of childhood ALL (chALL), resistance to chemotherapeutic agents and, as a consequence, a dismal prognosis develops in a significant number of patients. Therefore, there are urgent needs to have robust, sensitive, and disease-specific molecular prognostic and predictive biomarkers, which could allow better risk classification and then better clinical results. In this article, we review the currently known drug resistance biomarkers, including somatic or germ line nucleic acids, epigenetic alterations, protein expressions and metabolic variations. Moreover, biomarkers with potential clinical applications are discussed.

Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

“…The expression of lncRNAs as indicators of treatment response or relapse have gained significant attention in cancer research (reviewed in [ 89 , 90 ]). Understanding if lncRNA expression could serve as useful indicators of disease prognosis in B-ALL has also been investigated.…”

“…Drug resistance, whether intrinsic or acquired, is also a major problem in the management of ALL (reviewed in [ 89 ]). Glucocorticoids like dexamethasone and prednisone are critical in the treatment of B-ALL where they exhibit cytotoxic activity against hematological cells through the activation of apoptosis [ 100 ].…”

“…Additionally, prolonged use can lead to the emergence of glucocorticoid resistance. Studies have found that lncRNA expression may be functionally associated with drug resistance in acute leukemias [ 68 , 80 , 89 , 104 ]. For example, the lncRNA growth arrest-specific transcript 5 (GAS5) is downregulated in many cancers and may be used as a potential marker of treatment response in remission induction therapy for children with ALL [ 81 , 82 , 105 ].…”

Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

“…The expression of lncRNAs as indicators of treatment response or relapse have gained significant attention in cancer research (reviewed in [89,90]). Understanding if lncRNA expression could serve as useful indicators of disease prognosis in B-ALL has also been investigated.…”

“…Additionally, prolonged use can lead to the emergence of glucocorticoid resistance. Studies have found that lncRNA expression may be functionally associated with drug resistance in acute leukemias [68,80,89,104]. For example, the lncRNA growth arrest-specific transcript 5 (GAS5) is downregulated in many cancers and may be used as a potential marker of treatment response in remission induction therapy for children with ALL [81,82,105].…”