Using the Epigenetic landscape to explain Myeloma

Multiple myeloma is still an unstable cancer of plasma cells residing in bone marrow that leads to active infection through resistance to treatment. The molecular mechanisms that drive rescue progression and disease are not fully understood.

In December Meaningful Meeting of the American Hematology Association (ASH), data have suggested that several independent combinations of genetic and epigenetic events alter the balance of major epigenetic regulatory cycles, leading to genome-wide transcription reprogramming.

In this prohibition MedPage today video, study author Rafael Renatino-Canevarolo, PhD, a postdoctoral fellow at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, discusses the findings.

He has a transcript of his following remarks:

My name is Rafael Renatino-Canevarolo, a postdoc at Moffitt, and my work is called “Dynamic Epigenetic Landscapes Explaining the Complex Progression of Myeloma and Resistance to Drugs.”

In our work presented at ASH 2020, we studied multiple myeloma, which is a plasma cell cancer. We do not yet know exactly what causes the disease and drug resistance, and the problem is because of this, multiple myeloma is an incurable disease.

By studying a large group of patients treated at Moffitt, more than a thousand patients, we are able to see different patterns in gene expression of these cells. And we saw, for example, that cell identity-related pathways were reduced when myeloma started, while cell-related pathways and cell cycle were increased during drug resistance. And later, we tried to figure out what might be driving this.

And we found that there were some epigenetic markers and histones that surround the DNA, and these markers were differentially targeted at disease stages. We tested in 10 myeloma samples with different levels of disease using a method called single-cell ATAC-seq [Assay for Transposase Accessible Chromatin-sequencing].

And later, we can map these changes to various specific superficial transcription factors related to plasma cell identity. And we saw that some of them were reduced when myeloma started and many others were increased when they were drug resistant.

So we came up with this bowtie model in which we could map many cytogenetic mutations and anomalies with this reprogramming of what we call the epigenome, leading to an increase or decrease of the this biological pathway I mentioned is associated with myeloma onset and with drug. struggle against.