Prognostic Impact and Phenotype of Residual Acute Myeloid Leukemia Stem Cells
Background:
Leukemia stem cells (LSCs) have been demonstrated to be more therapy-resistant than leukemic blast cells reflecting measurable residual disease (MRD). CD34+CD38- cell frequency is an independent factor for relapse prediction and could therefore be used in the future to improve MRD assessment in acute myeloid leukemia (AML). This protocol is designed to enable accurate and reproducible immunophenotypic detection of measurable residual stem cell disease necessary for proper therapeutic decision and report their prognostic value in AML patients.
Methods:
Fifty-four Novo AML adult patients diagnosed in the onco-hematology service of the "20 August 1953" Hospital in Casablanca. We analyzed phenotype and frequency of CD45dim CD34+CD38- cells in bone marrow samples from patients with AML and non-myeloid malignancies using six-color flow cytometry and a simple one-tube essay.
Results:
For evaluation of leukemic stem cells, our gate strategy was based on the selection of CD34+CD38 - stem cells and leukemia associated immunophenotype approach. Positivity of CD123 or/and aberrant expression of primitive markers CD117 and HLA DR on stem cells discriminate leukemia stem cells from normal hematopoietic stem cells. We reported a statistically significant difference between expressions of primitive markers (CD117 and HLA DR) on leukemic stem cells. In addition, the frequency of LSCs after complete remission in post-induction was persistent in 50% of AML patients.
Conclusions:
Overall, we show that CD34+CD38-CD123+ as a basic phenotype, with aberrant phenotype detection of HLA DR and CD117 markers on stem cells, contributes to detecting LSCs which indicates the poor prognosis.
Insights
Leukemia stem cells (LSCs) are therapy-resistant and predict relapse in acute myeloid leukemia (AML). Detecting CD34+CD38-CD123+ LSCs with aberrant HLA DR and CD117 markers aids prognosis.
Area of Science:
- Hematology
- Immunology
- Cancer Research
Background:
- Leukemia stem cells (LSCs) exhibit higher therapy resistance than leukemic blast cells, contributing to measurable residual disease (MRD).
- The frequency of CD34+CD38- cells is a significant predictor of relapse in acute myeloid leukemia (AML).
- Accurate assessment of MRD is crucial for therapeutic decisions in AML patients.
Purpose of the Study:
- To develop a protocol for accurate and reproducible immunophenotypic detection of measurable residual stem cell disease in AML.
- To evaluate the prognostic value of LSCs in AML patients.
- To identify specific markers for distinguishing LSCs from normal hematopoietic stem cells.
Main Methods:
- Analysis of phenotype and frequency of CD45dim CD34+CD38- cells in bone marrow samples from 54 adult AML patients.
- Utilized six-color flow cytometry and a one-tube assay for immunophenotypic analysis.
- Gating strategy focused on CD34+CD38- stem cells and leukemia-associated immunophenotypes.
Main Results:
- Leukemia stem cells (LSCs) were identified as CD34+CD38- cells with positivity for CD123 and/or aberrant expression of CD117 and HLA DR.
- A statistically significant difference was observed in the expression of primitive markers (CD117 and HLA DR) on LSCs.
- LSCs persisted after complete remission in 50% of AML patients post-induction.
Conclusions:
- The phenotype CD34+CD38-CD123+ combined with aberrant HLA DR and CD117 expression effectively detects LSCs.
- Detection of these LSCs is indicative of a poor prognosis in AML patients.
- This immunophenotypic approach enhances MRD assessment for improved therapeutic strategies in AML.
More Related Videos
09:57Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia
Published on: March 5, 2018
09:44Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia
Published on: September 5, 2019
Related Concept Videos
Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Multipotency of Hematopoietic Stem Cells
Lineage Commitment
Differentiation of Common Myeloid Progenitor Cells
