Scientists from the Weizmann Institute isolate rare circulating hematopoietic stem cells and apply single-cell genetic sequencing in a blood test to detect myelodysplastic syndrome and assess leukemia risk, potentially replacing bone marrow biopsy and enabling earlier intervention.
Key points
Teams at the Weizmann Institute capture rare circulating CD34+ hematopoietic stem cells in peripheral blood.
Single-cell genetic sequencing identifies somatic mutations linked to myelodysplastic syndrome and leukemia.
Blood‐based assay predicts MDS severity and leukemia risk, replacing invasive bone marrow biopsy.
Why it matters:
A noninvasive blood test for early leukemia risk could transform diagnosis, enabling timely therapy and reducing reliance on invasive bone marrow biopsies.
Q&A
What is myelodysplastic syndrome?
Why are circulating stem cells important?
How does single-cell genetic sequencing work?
What is clonal hematopoiesis?
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Academy
Clonal Hematopoiesis and Aging
Clonal hematopoiesis refers to the process by which blood-forming stem cells acquire genetic mutations over time and expand to form a dominant clone in the bloodstream. As we age, our bone marrow stem cells divide repeatedly, and each division carries a small risk of acquiring errors in DNA. When a mutation confers a growth advantage—such as increased self-renewal—it allows that mutant cell to outcompete its neighbors, creating a ‘clone’ of genetically similar cells.
This age-related phenomenon is more common after age 50, affecting an estimated 10–20% of individuals. While many people with clonal hematopoiesis remain healthy, certain mutations—especially in genes like DNMT3A, TET2, and ASXL1—can increase risks of blood cancers, cardiovascular events, and other age-associated diseases. Monitoring clonal populations in blood can serve as an early warning for these conditions.
- Key genes: DNMT3A, TET2, ASXL1
- Prevalence: Increases from under 1% in under-40s to 10–20% over 50
- Clinical significance: Linked to higher risk of leukemia and heart disease
Myelodysplastic Syndrome (MDS)
Myelodysplastic syndrome is a group of disorders marked by dysfunctional blood cell production in the bone marrow. In MDS, hematopoietic stem cells fail to mature into healthy red blood cells, white blood cells, or platelets. Patients experience symptoms such as fatigue (due to anemia), increased infection risk (low white cell counts), and bleeding (low platelet counts).
MDS can arise de novo or as a result of previous chemotherapy. It is classified by severity based on the percentage of blasts (immature cells) in bone marrow and the presence of cytogenetic abnormalities. Importantly, up to one-third of MDS cases progress to acute myeloid leukemia (AML), making early detection crucial.
- Symptoms: Fatigue, infections, easy bruising
- Diagnosis: Traditionally requires bone marrow biopsy and cytogenetics
- Treatment: Supportive care, growth factors, hypomethylating agents, stem cell transplant
Single-Cell Genetic Sequencing
Single-cell sequencing is a powerful technique that analyzes the genome, transcriptome, or epigenome of individual cells rather than bulk tissue. In a typical workflow, cells are isolated (e.g., via fluorescence-activated cell sorting), lysed individually, and their genetic material amplified. High-throughput sequencing then profiles mutations or gene expression in each cell.
This approach uncovers cellular heterogeneity—differences between cells that bulk methods would mask. In the context of hematopoiesis, sequencing rare circulating stem cells reveals clonal architecture and mutation burdens directly from blood, enabling noninvasive diagnosis of MDS and risk stratification for leukemia.
- Applications: Cancer diagnostics, developmental biology, immunology
- Advantages: Resolves cell-to-cell variation, detects rare clones
- Limitations: Higher cost, computational complexity