Stamping Bar Codes on Cells to Solve Medical Mysteries - article.

[Lavinia-Blue]

An interesting article. Here's the link nytimes.com/2021/11/29/heal...

or google Stamping Bar Codes on Cells to Solve Medical Mysteries

[AussieNeil Administrator]

Non paywalled access:

vervetimes.com/stamping-bar...

Referenced papers:-

1) Colorful clones in the blood describes the development of the cell stamping technology. Note that the myeloid stem cell line was used in the original study. This stem cell line produces red blood cells, platelets, neutrophils and other white blood cells other than lymphocytes, which come from the lymphoid stem cell line.

science.org/doi/10.1126/sci...

2) Clonal dynamics of native haematopoiesis

It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear.

ncbi.nlm.nih.gov/pmc/articl...

With respect to the mention of CLL in the article introduction and later;

In the case of CLL above, Dr. Vijay Sankaran at Boston Children’s Hospital and his colleagues bar coded human cancer cells by taking advantage of innocuous, naturally occurring mutations that mark individual cells and are inherited by their progeny.

Bar coding, Dr. Sankaran said, “starts to give us a view of cancer that we never had before.”

Here is the abstract of Dr Sankaran's research which was not referenced in the New York Times article:

Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History

We employ mitochondrial single-cell assay for transposase-accessible chromatin with sequencing to profile 163,279 cells from 9 patients with chronic lymphocytic leukemia (CLL) collected across disease course and utilize mitochondrial DNA (mtDNA) mutations as natural genetic markers of cancer clone.

pubmed.ncbi.nlm.nih.gov/341...

As we know too well, CLL has a reputation of being incurable. About 15 years ago, one theory was that CLL regrew from CLL stem cells in the bone marrow resistant to the treatment drugs used. In the last decade, the theory has shifted to CLL regrowing from CLL cells that developed resistance to the treatment drugs or remained inactive during treatment and hence survived. Dr Sankaran's primary research fields appear to be haematopoiesis with a focus on childrens' cancer, not adult cancers, so I suspect the journalist extrapolated more out of their interview with Dr Sankaran than was intended.

I'd appreciate gardening-girl 's input on this.

Irrespective, this bar coding technology could prove a useful additional tool for studying the drivers of clonal evolution, from which curative treatments for CLL and other cancers could be developed.

Neil

[Lavinia-Blue in reply to AussieNeil]

Thanks for posting another link to the article. I do not have a subscription to NYT, yet the article was available—no pay wall—hmm.

I sure hope we can find the underlying cause of the surviving CLL cells and/or CLL Stem Cells.

[gardening-girl in reply to AussieNeil]

I agree that bar coding technology can provide very useful information. The NYT article was very interesting. Thanks Lavinia-Blue for posting.

As AussieNeil said, it is not clear why Dr Sankaran was the author interviewed for this article. He was one of 20 authors, and not one of the authors who specialize in CLL. The CLL specialist authors that I recognize are Matthew Davids, Jennifer Brown & Catherine Wu.

The paper cited by the NYT article "Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History" pubmed.ncbi.nlm.nih.gov/341... is basically a technical paper pointing to the benefit of using naturally occurring mutations in mitochondrial DNA to track CLL clones instead of using, for example, the sequence of the B cell receptor to track clones.

The paper acknowledges that bar coding is not new and that they are just targeting a different set of DNA sequences.

“Clonal tracking with mtscATAC-seq is an alternative to other DNA- and RNA-based single-cell approaches that utilize somatic nuclear mutations as natural barcodes.”

In reading the entire paper I did not see how the mystery cited below in the NYT article was solved.

“No one really knew why some patients with a white blood cell cancer called chronic lymphocytic leukemia, or CLL, relapsed after treatment and got a second cancer. Were some cancer cells just resistant?"

"An unexpected answer to this mystery has been found using a new technique that researchers call bar coding: The treatment does not always target the right cells.”

As I said I did not find any discussion of this in Dr Sankaran's paper.

Furthermore the NYT author apparently does not know that tracking cells using DNA sequences is not new and that calling the tracking "bar coding" is not new!

gardening-girl