The survival of patients with hematological malignancies has improved significantly over the last decades. This success is primarily the result of intensified chemotherapy treatments. However, this also results in numerous detrimental short- and long-term health effects due to their action in both leukemic and non-leukemic cells. Furthermore, for those leukemia patients that relapse, the prognosis remains extremely poor. Relapse has in part been explained by the presence of Leukemia Stem Cells (LSCs), a low-frequency subpopulation of leukemia cells possessing stem cell properties like self-renewal, multipotency and drug resistance.
Currently, intensification of current chemotherapies has reached their limit of toxicity, and so urgent clinical need remains to develop new therapies that specifically target the malignant cell population, in particular those cells that are responsible for relapse, while sparing their healthy peers.
When Hematopoietic Stem Cells (HSCs) undergo differentiation and rapid expansion to produce progenitor and finally mature cells, genetic lesions can occur that either directly lead to leukemia or provide a permissive landscape for the accumulation of additional mutations that results in leukemia. Identifying the cellular origins of both myeloid and lymphoid leukemia in pediatric and adult populations, as well as characterizing the LSC population, has been the subject of extensive research. General phenotypic characteristics of LSC have been identified in AML, including their drug resistance capacity as well as their restriction to a specific LSC niche. Indeed, LSC microenvironment is likely to protect them from genotoxic drugs, representing a potential cause of failure and relapse. However, LSC population in ALL remains poorly defined and debate remains on whether it exists. Therefore, an improved understanding on the cellular origins of leukemia and the molecular mechanisms that transform normal HSCs into LSCs remain active areas of research. Besides, LSCs genetics and a clear definition of their phenotype need to be addressed, as well as microenvironment interactions and their role in drug resistance. The development of therapeutics that specifically target LSCs are limited but urgently required if we are to avoid disease relapse and eventually cure all hematological malignancies.
This Research Topic focuses on the fundamental biology of both Hematopoietic and Leukemia Stem Cells. This includes HSC self-renewal capacity and maintenance, as well as its interaction with microenvironment. The origin of LSC and the molecular pathways involved in this process are other key aspects to be deciphered, as well as the identification of new markers defining leukemia initiating cells (LICs) population. Special interest is given to submissions that cover mechanisms of LSCs drug resistance and maintenance including but not limited to metabolic, genetic and/or epigenetic reprogramming, as well as potential therapies targeting LICs population including the LSC niche and its interaction with leukemic cells. Different article types will be considered for this Topic, including original Research articles, reviews, Methods articles or Brief Research Reports.
The survival of patients with hematological malignancies has improved significantly over the last decades. This success is primarily the result of intensified chemotherapy treatments. However, this also results in numerous detrimental short- and long-term health effects due to their action in both leukemic and non-leukemic cells. Furthermore, for those leukemia patients that relapse, the prognosis remains extremely poor. Relapse has in part been explained by the presence of Leukemia Stem Cells (LSCs), a low-frequency subpopulation of leukemia cells possessing stem cell properties like self-renewal, multipotency and drug resistance.
Currently, intensification of current chemotherapies has reached their limit of toxicity, and so urgent clinical need remains to develop new therapies that specifically target the malignant cell population, in particular those cells that are responsible for relapse, while sparing their healthy peers.
When Hematopoietic Stem Cells (HSCs) undergo differentiation and rapid expansion to produce progenitor and finally mature cells, genetic lesions can occur that either directly lead to leukemia or provide a permissive landscape for the accumulation of additional mutations that results in leukemia. Identifying the cellular origins of both myeloid and lymphoid leukemia in pediatric and adult populations, as well as characterizing the LSC population, has been the subject of extensive research. General phenotypic characteristics of LSC have been identified in AML, including their drug resistance capacity as well as their restriction to a specific LSC niche. Indeed, LSC microenvironment is likely to protect them from genotoxic drugs, representing a potential cause of failure and relapse. However, LSC population in ALL remains poorly defined and debate remains on whether it exists. Therefore, an improved understanding on the cellular origins of leukemia and the molecular mechanisms that transform normal HSCs into LSCs remain active areas of research. Besides, LSCs genetics and a clear definition of their phenotype need to be addressed, as well as microenvironment interactions and their role in drug resistance. The development of therapeutics that specifically target LSCs are limited but urgently required if we are to avoid disease relapse and eventually cure all hematological malignancies.
This Research Topic focuses on the fundamental biology of both Hematopoietic and Leukemia Stem Cells. This includes HSC self-renewal capacity and maintenance, as well as its interaction with microenvironment. The origin of LSC and the molecular pathways involved in this process are other key aspects to be deciphered, as well as the identification of new markers defining leukemia initiating cells (LICs) population. Special interest is given to submissions that cover mechanisms of LSCs drug resistance and maintenance including but not limited to metabolic, genetic and/or epigenetic reprogramming, as well as potential therapies targeting LICs population including the LSC niche and its interaction with leukemic cells. Different article types will be considered for this Topic, including original Research articles, reviews, Methods articles or Brief Research Reports.