Nature: Single-cell sequencing opens up a new way to cure leukemia

Acute myeloid leukemia (AML) is a type of malignant clonal disease that originates from leukemia stem cells (LSC), but it is difficult to separate due to the low abundance of cancer stem cells and the high similarity to healthy hematopoietic stem cells (HSC).

Recently, researchers from the Spanish Center for Genome Regulation (CRG) and the European Molecular Biology Laboratory (EMBL) published an article titled "Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell" in "Nature Communications" The article "transcriptomics" brings a new method of treating leukemia based on single-cell multi-omics, laying the foundation for people to find drugs to eliminate cancer from the source.

As we all know, most cancerous tissues are composed of rapidly dividing cells, and most cells have the ability to self-renew and stop multiplying after a certain number of divisions.

In this study, the researchers used a "MutaSeq" single-cell sequencing method that amplified nuclear mutations from cDNA to perform deep exon sequencing on leukemia patients, and based on the expression of CD34 + cells in the patient, The system compares the performance differences between MutaSeq and the whole transcriptome single-cell RNA sequencing method "Smart-seq2".

It was found that MutaSeq effectively covered the mitochondrial genome in single-cell RNA sequencing experiments, and compared with Smart-seq2, it provided better coverage of genomic target sites.

Subsequently, the researchers performed single-cell multi-omics MutaSeq data analysis on the bone marrow samples of four leukemia patients to determine whether a single cell in the patient was a stem cell, and used the somatic mutation lineage of mitochondria to track whether the stem cell was cancerous.

The study found that this method successfully identified and distinguished leukemia stem cells, pre-leukemia stem cells and healthy hematopoietic stem cells in the human body, thereby achieving a clear separation between healthy clones and cancerous clones.

So far, a large number of small molecule drugs have been proven to have clinical safety, but it is a difficult task to determine which cancer or which patients these drugs are most suitable for.

Therefore, the researchers compared the gene expression of all leukemia stem cells (pre-leukemia stem cells) and non-leukemia cells based on single-cell sequencing, and identified potential markers or drug targets in all leukemia cells.

At present, the research team has recruited a large number of clinical researchers from Germany and Spain, aiming to apply this method to larger-scale clinical research.

Reference materials:

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