Prognostic Impact and Phenotype of Residual Acute Myeloid Leukemia Stem Cells

Clinical Laboratory
|June 15, 2022
PubMed
Abstract

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.

Related Concept Videos

Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.0K
Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.2K
Lineage Commitment01:21

Lineage Commitment

Commitment is the  process whereby stem cells:
3.1K
Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.3K