identified cells responsible for relapses – breaking latest news

A study published in the journal Nature Communications sheds new light on the heterogeneous effects of chemotherapy on cells from patients with acute myeloid leukemia (AML). The authors are doctors and researchers from Irccs San Raffaele, SR-Tiget and Universit Vita-Salute San Raffaele. The research, carried out thanks to the support of the Airc Foundation, made use of innovative RNA sequencing techniques and new bioinformatics approaches. By studying in detail the tumor cells of patients and animal models during the first administration of chemotherapy, they discovered a rare population of leukemia stem cells, already present at the time of diagnosis, which condition the lack of response to therapy. Subsequently they developed a molecular signature, composed of a panel of genes useful for characterizing these rare leukemia stem cells already at the time of diagnosis, in order to identify them promptly to offer alternative therapies and better personalization of treatment. Acute myeloid leukemia an aggressive pathology that most likely affects people over 60, but can also occur in children and younger people. Current treatments can bring the disease to remission but a considerable percentage of adult patients relapse after treatment standard. Recent data suggested that relapse often originated from cells already present at diagnosis, difficult to distinguish from the leukemic mass. Furthermore, the mechanism used by these cells to relapse was not known.

I study

The first author, Matteo Naldini, a researcher at SR-Tiget explains: We started from serial clinical samples (i.e. analyzed at diagnosis, along the course of therapy and at relapse) of 13 patients with acute myeloid leukemia (AML) stored in the Biobank of the San Raffaele Hospital and we analyzed them with an innovative technology called RNA sequencing at the single cell level (scRNAseq) which made it possible to obtain the expression levels of thousands of genes for each single cell (their transcriptome). The development of new bioinformatics approaches has made it possible to specifically identify leukemia cell-associated transcriptomes, distinguishing them from normal blood cells, which coexist with residual disease after chemotherapy and cannot be reliably distinguished by standard technology. Adds Professor Bernhard Gentner, until recently head of the Stem Cells and Leukemia Laboratory of the San Raffaele Telethon Institute for Gene Therapy and now a lecturer at the University of Lausanne: For the first time we have described in great depth the effects of chemotherapy on leukemia cells that were highly heterogeneous: some died, some proliferated, and still others relapsed into a deep state of quiescence. By applying genetic engineering techniques to laboratory mice, the next step was to identify, in a significant percentage of patient samples, a rare population of leukemia stem cells, already present at the time of diagnosis, which condition the lack of response to therapy. Identifying this rare cell population was like finding a needle in a haystack and would not have been possible with standard techniques that detect only the “average response” of the entire leukemia population, Gentner concludes.

The prospects

The prospect for the future is to systematically introduce the search for these cells at the time of diagnosis, thus being able to identify patients who may not benefit from classic chemotherapy and immediately offer them an alternative approach based on epigenetic and targeted drugs. Says Professor Fabio Ciceri, director of the Hematology and Bone Marrow Transplantation Unit and director of the Cancer Center of the IRCCS San Raffaele Hospital: These results provide a new tool to make treatments more precise and targeted, which adds to existing molecular markers in defining the severity of the disease and planning the treatment path.