scholarly journals Selective Targeting of Unique Metabolic Properties of Leukemic Stem Cells in Acute Myeloid Leukemia

Author(s):  
Benjamin Brakel

Current therapeutic options in the treatment of acute myeloid leukemia often succumb to high instances of relapse and subsequent mortality. Chemotherapy and radiotherapy have long been used as the standard treatment for this disease, remaining stagnant over the past few decades. Recently, a small self-renewing population of leukemic stem cells have been identified as drivers of cancer relapse and progression due to their increased resistance to anticancer therapeutics. This enables these cells to maintain a minimal residual disease and results in downstream differentiation, leading to relapse. Targeting these cells may lead to effective therapies that reduce relapse and mortality. Recently, the metabolic properties of leukemic stem cells have begun to be elucidated. Here, we discuss recent discoveries regarding the metabolism of leukemic stem cells and approaches to targeting their unique metabolic properties.  

2021 ◽  
Vol 11 ◽  
Author(s):  
Noortje van Gils ◽  
Fedor Denkers ◽  
Linda Smit

Standard induction chemotherapy, consisting of an anthracycline and cytarabine, has been the first-line therapy for many years to treat acute myeloid leukemia (AML). Although this treatment induces complete remissions in the majority of patients, many face a relapse (adaptive resistance) or have refractory disease (primary resistance). Moreover, older patients are often unfit for cytotoxic-based treatment. AML relapse is due to the survival of therapy-resistant leukemia cells (minimal residual disease, MRD). Leukemia cells with stem cell features, named leukemic stem cells (LSCs), residing within MRD are thought to be at the origin of relapse initiation. It is increasingly recognized that leukemia “persisters” are caused by intra-leukemic heterogeneity and non-genetic factors leading to plasticity in therapy response. The BCL2 inhibitor venetoclax, combined with hypomethylating agents or low dose cytarabine, represents an important new therapy especially for older AML patients. However, often there is also a small population of AML cells refractory to venetoclax treatment. As AML MRD reflects the sum of therapy resistance mechanisms, the different faces of treatment “persisters” and LSCs might be exploited to reach an optimal therapy response and prevent the initiation of relapse. Here, we describe the different epigenetic, transcriptional, and metabolic states of therapy sensitive and resistant AML (stem) cell populations and LSCs, how these cell states are influenced by the microenvironment and affect treatment outcome of AML. Moreover, we discuss potential strategies to target dynamic treatment resistance and LSCs.


2016 ◽  
Vol 45 ◽  
pp. 1-7 ◽  
Author(s):  
Hao Ho ◽  
Alyza M. Skaist ◽  
Aparna Pallavajjala ◽  
Raluca Yonescu ◽  
Denise Batista ◽  
...  

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