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Integrated next-generation sequencing system cuts down turnaround times to offer reliable precision treatment to leukemia patients.
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Rapid NGS System to Improve AML Precision Treatment

 Integrated genomics-based system detects some 92 percent genetic variants in validated assays

The Journal of Molecular Diagnostics
Published:Feb 07, 2023
|3 min read
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PHILADELPHIA, PA — Identifying recurrent genetic alterations in myeloid neoplasms has improved diagnosis and expanded targeted treatments available to patients. However, treatment initiation can be delayed by the variable and lengthy turnaround times involved in testing for these alterations. 

In a novel study, researchers evaluated an integrated next-generation sequencing (NGS) system and found that it can deliver accurate, genomics-based diagnoses to accelerate time to precision therapies, thus benefiting patient outcomes. Their results appear in The Journal of Molecular Diagnostics, published by Elsevier.

In myeloid neoplasms, the bone marrow produces too many or too few red blood cells, platelets, or certain white blood cells. The discovery of recurrent genetic alterations in myeloid neoplasms has improved diagnostic accuracy and expanded the targeted treatment options available to patients. This progress is especially relevant in improving the treatment of acute myeloid leukemia (AML), for which there is currently a dismal 30.5 percent relative five-year survival rate.

Current National Comprehensive Cancer Network (NCCN) guidelines now endorse genetic testing for AML. Recently, a number of drug-targeted therapies relying on the presence or absence of specific gene alterations have emerged. These drugs are used not only for relapsed or refractory disease but also as a component of induction chemotherapy for certain patients.

“The successful implementation of these therapies relies on immediate knowledge of the leukemia’s genetic features,” explained Kojo S.J. Elenitoba-Johnson, MD, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, NY, who was at the Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, PA, as the lead investigator at the time the study was conducted.

The problem

Determining leukemia’s genetic features involves testing for recurrent, diagnostically, and therapeutically relevant genetic alterations. Unfortunately, current diagnostic tools use multiple technologies, different domains of expertise, and unconnected workflows, resulting in markedly variable and lengthy turnaround times that can delay treatment.

“NGS is a powerful tool capable of identifying most of these alterations; however, current NGS platforms and bioinformatics bottlenecks represent significant barriers to an optimal and timely diagnosis, with turnaround times often exceeding ten to 14 days, thereby delaying treatment decisions,” Elenitoba-Johnson noted. “As a result, laboratories typically perform redundant testing to support a more rapid turnaround time for key variants.”

The study and the solution: An integrated NGS system

To address the need for identifying these alterations more efficiently, investigators evaluated the Oncomine™ Myeloid Assay GX panel on the Ion Torrent Genexus platform, a rapid (turnaround time less than 24-hour nucleic acid to result) integrated nucleic acid NGS platform for detecting clinically relevant genetic aberrations in myeloid disorders. 

Specimens included synthetic DNA (101 targets) and RNA (nine targets) controls and real-world nucleic acid material derived from bone marrow or peripheral blood samples (40 patients). Clinical DNA and RNA samples were retrospectively identified from blood or bone marrow specimens that had already undergone nucleic acid extraction and genetic testing in a Clinical Laboratory Improvement Amendments (CLIA) certified clinical laboratory following previously validated protocols.

Results and performance indices were compared with those obtained from clinically validated genomic testing workflows in two separate clinical laboratories. The assay identified 100 percent of DNA and RNA control variants. For specimens derived from patients, it reported 82 of 107 DNA variants and all of the 19 RNA gene fusions identified on clinically validated assays, yielding an overall 80 percent detection rate.

Reanalysis of exported, unfiltered data revealed 15 DNA variants that were not initially identified, yielding an overall 92 percent potential detection rate.

These results are promising for implementing an integrated NGS system to rapidly detect genetic aberrations, facilitating accurate, genomics-based diagnoses, and accelerating precision therapies in myeloid neoplasms.

“There are significant laboratory workflow benefits using this platform compared with the current testing methods,” commented Elenitoba-Johnson. “Automated and integrated work?ow-based platforms that deliver clinically relevant results in less than 24 hours could revolutionize the diagnostic workup of neoplastic conditions, potentially improving patient outcomes. The availability of accurate results in clinically relevant timescales will enable deployment of genomic studies in the frontline for diagnostic evaluation of patients. Automated work?ows such as these will improve operational ef?ciency and have signi?cant economic impact on laboratory expenses given the reduced requirement for human involvement in carrying out the laboratory tests.”

- This press release was originally published on The Journal of Molecular Diagnostics website