We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Technopath Clinical Diagnostics - An LGC Company

Fluidigm

Fluidigm Corporation focuses on the most pressing needs in translational and clinical research, including cancer, imm... read more Featured Products: More products

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Epigenomic Biomarker Predict CAR T-Cell Therapy Resistance in Pediatric Leukemia

By LabMedica International staff writers
Posted on 18 Apr 2022
Print article
Image: Fluidigm CyTOF2 Mass Cytometer (Photo courtesy of University of Minnesota)
Image: Fluidigm CyTOF2 Mass Cytometer (Photo courtesy of University of Minnesota)

Children with acute lymphoblastic leukemia (ALL) whose cells express an epigenomic biomarker rooted in DNA methylation patterns may be less likely to respond to CD19-directed CAR T-cell therapy.

CAR T-cell therapy is a type of immunotherapy in which immune cells called T cells are harvested from a patient, reprogrammed to target cancer cells, and infused back into the patient to fight the cancer. A common CAR T-cell target is the receptor CD19; however, cancer cells can mutate CD19 or suppress its expression to develop CAR T resistance. While CD19 expression is currently one of the few biomarkers of potential CAR T response, not all patients who develop resistance lose CD19 expression.

Medical Scientists collaborating with the Seattle Children's Hospital (Seattle, WA, USA) acquired pretreatment bone marrow samples from the PLAT-02 clinical trial. The samples were collected from seven patients who experienced a complete remission following CD19-targeted CAR T therapy and seven patients who did not have a response, defined by continued evidence of circulating leukemia cells 63 days post-treatment. The team performed extensive studies, including whole-exome sequencing, bulk RNA-sequencing, long-read sequencing of the CD19 locus, array-based methylation testing, ATAC sequencing, single-cell RNA sequencing, and CyTOF mass cytometry (Fluidigm, South San Francisco, CA, USA).

The investigators reported that they found 238 regions of increased DNA methylation in patients who did not respond to treatment, and further determined that the pre-treatment methylation patterns were those known to be turned off by polycomb repressive complex 2 (PRC2) repression in stem cells. They then did a gene set enrichment analysis of their ATAC sequencing data and saw increased accessibility of chromatin at regions known to be associated with proliferation and cell cycling in stem cells.

The team also identified decreased expression of genes involved in antigen presentation and processing, pathways that are crucial for mounting an immune response, in cells that did not respond to CAR T therapy. Decreased antigen presentation could indicate that, even if leukemia cells continue to express CD19, they may not effectively process additional immune targets.

Javed Khan, MD, the senior author of the study said, “Interestingly, we saw subpopulations of cells expressing both lymphoid and myeloid markers, indicating that the epigenomes of some nonresponsive leukemias may contain a hybrid population of cells with a hybrid of ALL and AML epigenomes. Our data suggest that these leukemias, characterized by both lymphoid and myeloid-specific accessible regions, are likely less differentiated than responsive leukemia.” The study was presented at the American Association of Cancer Research's annual meeting held April 8-13, 2022, in New Orleans, LA, USA.

Related Links:
Seattle Children's Hospital 
Fluidigm 

New
Gold Supplier
NT-proBNP Quantitative Antigen Test
NT-proBNP-CHECK-1
New
Gold Supplier
Immunofluorescence Incubator
RaFIA Immunofluorescence Incubator
New
3-Part Diff Hematology Analyzer
DLB3
New
Silver Supplier
Receptor Destroying Enzyme
RDE II (Receptor Destroying Enzyme)

Print article

Channels

Clinical Chem.

view channel
Image: The analysis pipeline used to investigate associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease (Photo courtesy of University College London)

Lipid Measurements Show Potential as Alzheimer’s Disease Biomarkers

Brain changes accompanying ageing are varied and can include pathologies that lead to cognitive impairment, the commonest of which is Alzheimer’s disease (AD). Identifying blood-based signatures of brain... Read more

Molecular Diagnostics

view channel
Image: This image depicts a DNA molecule that is methylated on both strands on the center cytosine. DNA methylation plays an important role for epigenetic gene regulation in development and cancer (Photo courtesy of Wikimedia Commons)

Study Supports Use of Methylated DNA Biomarkers for Cancer Diagnosis and Prognosis

A recent study added weight to the theory that methylated DNA biomarkers could be used for cancer diagnosis and prognosis. Methylation is a biological process by which methyl groups are added to a DNA molecule.... Read more

Industry

view channel
Image: QIAGEN has acquired a majority stake in enzymes provider BLIRT S.A. (Photo courtesy of QIAGEN)

Qiagen Acquires Enzymes Provider Blirt to Strengthen Sample Technologies Business

QIAGEN N.V. (Venlo, Netherlands) has signed agreements to acquire a 96% majority ownership stake in BLIRT S.A. (Gdansk, Poland), a manufacturer of recombinant enzymes for the life science industry.... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.