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Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
230
Pathogenic Mechanisms in Acute Myeloid Leukemia
Sohini Chakraborty1, Christopher Y Park2
1Department of Pathology, New York University Grossman School of Medicine, New York, USA. Sohini.chakraborty@nyulangone.org.
Current Treatment Options in Oncology
|October 3, 2022
Summary
Acute myeloid leukemia (AML) involves cell-intrinsic genetic changes and cell-extrinsic microenvironment factors promoting disease. Understanding these mechanisms is key to developing more effective AML treatments and preventing relapse.
Area of Science:
- Hematology
- Cancer Biology
- Molecular Oncology
Background:
- Acute myeloid leukemia (AML) is the most common adult leukemia in the USA, causing the highest mortality.
- Despite initial remission rates, most AML patients experience disease relapse, highlighting a critical need for improved therapeutic strategies.
- Recent advancements in sequencing and disease modeling have significantly enhanced our comprehension of AML's molecular underpinnings.
Purpose of the Study:
- To elucidate the cell-intrinsic and cell-extrinsic mechanisms driving leukemogenesis in Acute myeloid leukemia.
- To identify key molecular alterations and microenvironmental interactions that contribute to AML development and progression.
- To explore how a deeper understanding of these mechanisms can inform the development of novel therapeutic interventions for AML.
Main Methods:
- Review and synthesis of current research on molecular mechanisms in AML.
- Classification of leukemogenic factors into cell-intrinsic and cell-extrinsic categories.
- Analysis of genetic and epigenetic alterations in hematopoietic stem/progenitor cells.
- Investigation of the role of the leukemic microenvironment in promoting AML progression and therapy resistance.
Main Results:
- Cell-intrinsic mechanisms involve genetic and epigenetic alterations leading to dysregulated gene expression and enhanced fitness of hematopoietic stem/progenitor cells.
- Cell-extrinsic mechanisms encompass interactions with the hematopoietic and non-hematopoietic stromal microenvironment, fostering leukemic clone survival, self-renewal, and therapy resistance.
- Therapy can select for specific leukemic clones that subsequently re-initiate disease, indicating a role for evolutionary dynamics in AML relapse.
Conclusions:
- A comprehensive understanding of both cell-intrinsic and cell-extrinsic factors is crucial for unraveling the complexities of AML.
- Targeting these identified mechanisms offers promising avenues for developing innovative treatments to overcome AML therapy resistance and prevent relapse.
- Further research into these pathways will pave the way for more effective strategies against Acute myeloid leukemia.
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