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Related Experiment Video

Updated: May 11, 2026

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up

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

The clones have STRACK: Tracing responses to leukemic mutations.

Eirini P Papapetrou¹

¹Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Institute of Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

|April 4, 2025

Summary

Researchers used genetic barcoding and sister-cell analysis to study how mutations affect hematopoietic stem cells (HSCs). This revealed intrinsic differences in cell behavior that influence leukemia development.

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Area of Science:

Hematology
Stem Cell Biology
Cancer Research

Background:

Hematopoietic stem cells (HSCs) are crucial for blood formation.
Leukemia arises from mutations in HSCs, but their intrinsic heterogeneity complicates understanding of disease initiation.
Previous studies lacked methods to track individual cell behaviors after acquiring mutations.

Purpose of the Study:

To investigate the impact of leukemia driver mutations on the behavior of individual murine hematopoietic stem cells (HSCs).
To understand how intrinsic cellular heterogeneity influences HSC fate decisions upon acquiring mutations.
To develop a method for capturing and analyzing clonal cell behaviors in the context of early leukemia development.

Main Methods:

Employing genetic barcoding to label individual HSCs and their progeny.
Utilizing ex vivo expansion to culture and observe HSC clones.
Performing sister-cell analysis to compare the fates of sibling cells with and without induced leukemia driver mutations.

Main Results:

Demonstrated significant heterogeneity in clonal cell behaviors among HSCs with identical mutations.
Identified specific behavioral differences that predispose certain HSC clones to leukemic transformation.
Showcased how intrinsic cell properties, not just mutations, dictate leukemia progression.

Conclusions:

Intrinsic cellular heterogeneity plays a critical role in leukemia initiation and progression.
The developed methodology allows for detailed analysis of clonal dynamics in stem cell mutations.
Understanding HSC heterogeneity is key to developing targeted therapies for leukemia.