Leukemia Stem Cell Frequency at Diagnosis Correlates With Measurable/Minimal Residual Disease and Impacts Survival in Adult Acute Myeloid Leukemia

Kamel, Azza M.; Elsharkawy, Nahla M.; Kandeel, Eman Z.; Hanafi, Marwa; Samra, Mohamed; Osman, Randa A.

doi:10.3389/fonc.2022.867684

Cited by 5 publications

(5 citation statements)

References 42 publications

(57 reference statements)

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“…The poor outcome of AML patients was associated with high CD34+CD38− cell frequency, characteristic of LSC, and may inform prognosis [103]. In a separate study, Kamel et al, highlighted that immunophenotypic LSC detection at diagnosis bears significant association with MRD status at early and late postinduction time points and can prognosticate patient outcome [123]. Persistent LSC clones observed during diagnosis may emerge as dominant clones during relapse, or potentially as preleukemic triggering clones via acquisition of new mutations, thus re-emerging as new subclonal populations [57,124].…”

Section: Lsc Detection As a Measure For Improving Mrd Sensitivitymentioning

confidence: 99%

Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection

Rajsri

Roy

Chakraborty

2023

Cancers

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Acute myeloid leukemia (AML) is a hematological malignancy characterized by an abundance of incompletely matured or immature clonally derived hematopoietic precursors called leukemic blasts. Rare leukemia stem cells (LSCs) that can self-renew as well as give rise to leukemic progenitors comprising the bulk of leukemic blasts are considered the cellular reservoir of disease initiation and maintenance. LSCs are widely thought to be relatively resistant as well as adaptive to chemotherapy and can cause disease relapse. Therefore, it is imperative to understand the molecular bases of LSC forms and functions during different stages of disease progression, so we can more accurately identify these cells and design therapies to target them. Irrespective of the morphological, cytogenetic, and cellular heterogeneity of AML, the uniform, singularly important and independently significant prognosticator of disease response to therapy and patient outcome is measurable or minimal residual disease (MRD) detection, defined by residual disease detection below the morphology-based 5% blast threshold. The importance of LSC identification and frequency estimation during MRD detection, in order to make MRD more effective in predicting disease relapse and modifying therapeutic regimen is becoming increasingly apparent. This review focuses on summarizing functional and cellular composition-based LSC identification and linking those studies to current techniques of MRD detection to suggest LSC-inclusive MRD detection as well as outline outstanding questions that need to be addressed to improve the future of AML clinical management and treatment outcomes.

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Section: Lsc Detection As a Measure For Improving Mrd Sensitivitymentioning

confidence: 99%

Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection

Rajsri

Roy

Chakraborty

2023

Cancers

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“…Increasing evidence indicates that the LSC frequency at diagnosis in AML patients is of prognostic relevance (Kamel et al, 2022; Terwijn et al, 2014; van Rhenen et al, 2005). The persistence of LSCs after treatment has been shown when assessing measurable residual disease (MRD) in AML patients (Gomez‐Arteaga & Guzman, 2018; Zeijlemaker et al, 2016).…”

Section: Leukaemia Stem Cells Are the Reservoir Of The Diseasementioning

confidence: 99%

“…The persistence of LSCs after treatment has been shown when assessing measurable residual disease (MRD) in AML patients (Gomez‐Arteaga & Guzman, 2018; Zeijlemaker et al, 2016). The evaluation of MRD constitutes the most important indicator of response to therapy in all types of acute leukaemia, which helps in the selection of therapy including the decision of stem cell transplantation (Gomez‐Arteaga & Guzman, 2018; Kamel et al, 2022).…”

Section: Leukaemia Stem Cells Are the Reservoir Of The Diseasementioning

confidence: 99%

Understanding the interaction between leukaemia stem cells and their microenvironment to improve therapeutic approaches

Martinez

Guzmán

2023

British J Pharmacology

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Although chemotherapeutic regimens can eliminate blasts in leukaemia patients, such therapies are associated with toxicity and often fail to eliminate all malignant cells resulting in disease relapse. Disease relapse has been attributed to the persistence of leukaemia cells in the bone marrow (BM) with the capacity to recapitulate disease; these cells are often referred to as leukaemia stem cells (LSCs). Although LSCs have distinct characteristics in terms of pathobiology and immunophenotype, they are still regulated by their interactions with the surrounding microenvironment. Thus, understanding the interaction between LSCs and their microenvironment is critical to identify effective therapies. To this end, there are numerous efforts to develop models to study such interactions. In this review, we will focus on the reciprocal interactions between LSCs and their milieu in the BM. Furthermore, we will highlight relevant therapies targeting these interactions and discuss some of the promising in vitro models designed to mimic such relationship.

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“…As an interleukin 3 (IL-3) receptor, the CD123 plays an important role in the production and function of healthy hematopoietic cells, but its overexpression in leukemic patients results in an adverse prognosis, with leukocytosis due to increased susceptibility to IL-3 and higher chemoresistance rates due to the high replication rate. In addition, mutations in DNMT3A and WT1 can also be strongly associated with CD123 [ 70 , 96 , 97 , 98 , 99 , 100 ].…”

Section: Immunophenotyping X Genetics In Amlmentioning

confidence: 99%

Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia

et al. 2023

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Acute myeloid leukemia (AML) is a hematologic malignancy that occurs due to alterations such as genetic mutations, chromosomal translocations, or changes in molecular levels. These alterations can accumulate in stem cells and hematopoietic progenitors, leading to the development of AML, which has a prevalence of 80% of acute leukemias in the adult population. Recurrent cytogenetic abnormalities, in addition to mediating leukemogenesis onset, participate in its evolution and can be used as established diagnostic and prognostic markers. Most of these mutations confer resistance to the traditionally used treatments and, therefore, the aberrant protein products are also considered therapeutic targets. The surface antigens of a cell are characterized through immunophenotyping, which has the ability to identify and differentiate the degrees of maturation and the lineage of the target cell, whether benign or malignant. With this, we seek to establish a relationship according to the molecular aberrations and immunophenotypic alterations that cells with AML present.

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Leukemia Stem Cell Frequency at Diagnosis Correlates With Measurable/Minimal Residual Disease and Impacts Survival in Adult Acute Myeloid Leukemia

Cited by 5 publications

References 42 publications

Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection

Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection

Understanding the interaction between leukaemia stem cells and their microenvironment to improve therapeutic approaches

Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia

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