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Updated: Aug 30, 2025
Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Chasing leukemia differentiation through induction therapy, relapse and transplantation
Jennifer N Saultz1, Jeffrey W Tyner2
1Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States of America; Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, United States of America.
Abstract:
Despite rapid advances in our understanding of acute myeloid leukemia (AML), the disease remains challenging to treat with 5-year survival for adult patients 20 years or older estimated to be 26% (Cancer 2021). The use of new targeted therapies including BCL2, IDH1/IDH2, and FLT3 inhibitors has revolutionized treatment approaches but also changed the disease trajectory with unique modes of resistance. Recent studies have shown that stem cell maturation state drives expression level and/or dependence on various pathways, critical to determining drug response. Instead of anticipating these changes, we remain behind the curve chasing the next expanded clone. This review will focus on current approaches to treatment in AML, including defining the significance of blast differentiation state on chemotherapeutic response, signaling pathway dependence, metabolism, immune response, and phenotypic changes. We conclude that multimodal treatment approaches are necessary to target both the immature and mature clones, thereby, sustaining drug response.
Insights
Acute myeloid leukemia (AML) treatment is challenged by evolving resistance. Targeting both immature and mature leukemia cells with multimodal therapies is crucial for sustained drug response and improved outcomes.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Acute myeloid leukemia (AML) remains a significant challenge, with a 5-year survival rate of 26% for older adults.
- Novel targeted therapies (e.g., BCL2, IDH1/IDH2, FLT3 inhibitors) have altered AML treatment but introduced unique resistance mechanisms.
Purpose of the Study:
- To review current AML treatment strategies.
- To define the impact of blast differentiation state on therapeutic response.
- To highlight the need for adaptive treatment approaches.
Main Methods:
- Review of recent studies on AML pathogenesis and treatment.
- Analysis of the role of stem cell maturation in drug response.
- Examination of signaling pathways, metabolism, immune response, and phenotypic changes in AML blasts.
Main Results:
- Stem cell maturation state influences pathway dependence and drug sensitivity.
- Current treatment strategies often lag behind evolving disease clones.
- Blast differentiation state significantly affects chemotherapeutic response, signaling, metabolism, and immune interactions.
Conclusions:
- Multimodal treatment strategies are necessary to address both immature and mature leukemia clones.
- Targeting diverse cellular states is essential for overcoming resistance and sustaining treatment efficacy in AML.
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