Impact of Leukemia Stem Cells Phenotype Expression on Response to Induction Therapy in Acute Myeloid Leukemia Patients

Almohsen, Faez Sh.; Al-Mudallal, Subh Salem

doi:10.2174/1871529x19666190719105954

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…CD123 is a marker expressed on LSCs (395,397,494), but not exclusively (395,398). In AML patients, CD123 expression correlates to the therapy response rate (413,495), the relapse risk (403), and a shorter disease-free period and OS (399,413). CD123 has been associated with increased proliferation and differentiation (494,496).…”

Section: Cd123 and Cd33mentioning

confidence: 99%

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

et al. 2020

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The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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Section: Cd123 and Cd33mentioning

confidence: 99%

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

et al. 2020

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“…Stem cells are undifferentiated cells with the ability to reproduce themselves (i.e., self-renew to maintain their cell population) and also to give rise to a range of distinct, specialized cells (i.e., differentiate into multiple cell types as needed) ( Slack, 2008 ; Huang et al, 2021 ; Shu et al, 2021 ). Stem and progenitor cell research has led to breakthrough developments in regenerative medicine, including stem cell-based therapies for various diseases (e.g., leukemia, aplastic anemia, osteopetrosis) ( Río et al, 2018 ; Almohsen and Al-Mudallal, 2020 ; Capo et al, 2020 ). Likewise, this knowledge has created new research fields, such as the generation of organoids.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Limb Assay as in Vivo Organoid Model

García-García

Garay-Pacheco

Marín-Llera

et al. 2022

Front. Cell Dev. Biol.

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Organ formation initiates once cells become committed to one of the three embryonic germ layers. In the early stages of embryogenesis, different gene transcription networks regulate cell fate after each germ layer is established, thereby directing the formation of complex tissues and functional organs. These events can be modeled in vitro by creating organoids from induced pluripotent, embryonic, or adult stem cells to study organ formation. Under these conditions, the induced cells are guided down the developmental pathways as in embryonic development, resulting in an organ of a smaller size that possesses the essential functions of the organ of interest. Although organoids are widely studied, the formation of skeletal elements in an organoid model has not yet been possible. Therefore, we suggest that the formation of skeletal elements using the recombinant limb (RL) assay system can serve as an in vivo organoid model. RLs are formed from undissociated or dissociated-reaggregated undifferentiated mesodermal cells introduced into an ectodermal cover obtained from an early limb bud. Next, this filled ectoderm is grafted into the back of a donor chick embryo. Under these conditions, the cells can receive the nascent embryonic signals and develop complex skeletal elements. We propose that the formation of skeletal elements induced through the RL system may occur from stem cells or other types of progenitors, thus enabling the study of morphogenetic properties in vivo from these cells for the first time.

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MRD Tailored Therapy in AML: What We Have Learned So Far

et al. 2021

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Acute myeloid leukemia (AML) is a heterogeneous clonal disease associated with a dismal survival, partly due to the frequent occurrence of relapse. Many patient- and leukemia-specific characteristics, such as age, cytogenetics, mutations, and measurable residual disease (MRD) after intensive chemotherapy, have shown to be valuable prognostic factors. MRD has become a rich field of research where many advances have been made regarding technical, biological, and clinical aspects, which will be the topic of this review. Since many laboratories involved in AML diagnostics have experience in immunophenotyping, multiparameter flow cytometry (MFC) based MRD is currently the most commonly used method. Although molecular, quantitative PCR based techniques may be more sensitive, their disadvantage is that they can only be applied in a subset of patients harboring the genetic aberration. Next-generation sequencing can assess and quantify mutations in many genes but currently does not offer highly sensitive MRD measurements on a routine basis. In order to provide reliable MRD results, MRD assay optimization and standardization is essential. Different techniques for MRD assessment are being evaluated, and combinations of the methods have shown promising results for improving its prognostic value. In this regard, the load of leukemic stem cells (LSC) has also been shown to add to the prognostic value of MFC-MRD. At this moment, MRD after intensive chemotherapy is most often used as a prognostic factor to help stratify patients, but also to select the most appropriate consolidation therapy. For example, to guide post-remission treatment for intermediate-risk patients where MRD positive patients receive allogeneic stem cell transplantation and MRD negative receive autologous stem cell transplantation. Other upcoming uses of MRD that are being investigated include: selecting the type of allogeneic stem cell transplantation therapy (donor, conditioning), monitoring after stem cell transplantation (to allow intervention), and determining drug efficacy for the use of a surrogate endpoint in clinical trials.

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Impact of Leukemia Stem Cells Phenotype Expression on Response to Induction Therapy in Acute Myeloid Leukemia Patients

Cited by 3 publications

References 8 publications

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Recombinant Limb Assay as in Vivo Organoid Model

MRD Tailored Therapy in AML: What We Have Learned So Far

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