TEST:

Archer® VariantPlex® Myeloid panel

DTA mutations detected with a clinically used NGS panel in patients with MPN are associated with increased risk of bleeding complications, as well as increased thrombotic risk in a subgroup of patients. These findings support the incorporation of molecular panel analyses in thrombosis and bleeding risk assessment in MPN, and merit further investigation.

A retrospective analysis of 535 clinical specimens tested with the Archer NGS panel showed a frequency and pattern of mutations across myeloid malignancies that were similar to other published studies. A review of the diagnostic classification of patients with acute myeloid leukaemia and myelodysplastic syndrome using the World Health Organisation 2017/2022 and International Consensus Classification 2022 guidelines, in addition to European LeukemiaNet 2017/2022 risk stratification of AML patients, was also performed to assess the utility of the molecular information provided by the Archer NGS panel.

Our study demonstrated that the sensitivity of WGS in detecting clinically relevant mutations is comparable to high-depth panel assays despite the overall lower coverage. Given that WGS is a truly unbiased genome-wide molecular profiling platform, our data further support the importance of WGS in oncology molecular diagnostics.

The Archer panel presented high performance and good coverage in GC-rich regions as CEBPA gene being a promising test in accuracy of somatic analysis and was validated in our laboratory.

Additional mutations were detected in 12.2% of 41 MPN-SVT patients, lower than reported elsewhere. Explanations for this include methodologic differences: the lower sensitivity of older NGS technologies and different thresholds for reporting abnormal NGS. The presence of additional mutations by NGS was associated with higher JAK2V617F VAF, whilst rising VAF was seen alongside clinical disease progression; these findings concur with those seen elsewhere.

Using a combination of flow cytometry, magnetic cell sorting, and NGS, variants specific to the tumor fraction of samples were identified. For patient specimens, the presence of ARCH/CHIP mutations in both enriched and residual cell populations indicate these variants evolved prior to the emergence of true leukemic progenitor cells; the identification of the flow-matched mutations only in the enriched population indicates the key role of these changes in the disease progression. Together, flow cytometry and cell-enriched NGS have the potential to enhance detection of disease-driving mutations earlier, thus, could be used as novel approaches to identify and treat myeloid neoplasms early with existing therapies and/or support development of new investigational agents.

"Integrated DNA Technologies, Inc....announced it closed on the purchase of Next Generation Sequencing (NGS) research assays from Invitae Corporation (NYSE: NVTA) under the trademarked name Archer. The integration of IDT’s portfolio with the acquired NGS research assays—which have been foundational in researching novel cancer fusions—will empower labs with an all-in-one solution to uncover biomarkers and advance cancer discoveries. The transaction enables IDT to expand its existing operations, build upon the legacy Archer portfolio, and welcome more than 100 new associates globally....Transaction Details-IDT purchased Archer NGS research assays—which reported high double-digit growth since 2019—from Invitae for cash consideration of approximately $48 million, subject to certain adjustments. The transaction is structured as an asset deal and includes a license to intellectual property related to the AMP technology."

"CH was associated with more A Fib and atherosclerosis in PCD patients, but overall survival was not significantly different for CH patients in the MM subgroup. Our data indicate an increase in CH prevalence with PCD disease progression highlighting the need for additional studies to evaluate the factors responsible."

Aims To test palbociclib and ponatinib, along with reference drugs – venetoclax, azacitidine, cytarabine+doxorubicine (chemotherapy) on 2 primary AML samples in a patient-derived xenograft model. Effect of ponatinib was only limited. This encourages further investigation of treatment efficacy in different AML subtypes and in combination with other drugs.

Our free web application can correctly create HGVS FLT3-ITD nomenclature from next generation sequencing results, as long as there is no error or mutation at the 3’ end of the sequence. RNA-based sequencing is required to definitively determine how the intronic sequence in ITD is translated into amino acids.

NMA is an automated sample-to-results workflow that can identify myeloid disorder-associated genomic variants in less than 48 hours from library preparation to clinical reporting. We show that NMA is highly concordant with a standard DNA NGS assay for detecting mutations within recurrently mutated AML genes. Accurate rapid genotyping is required for assignment to initial treatment with targeted therapy, and this technology may be a valuable tool for upcoming clinical trials for patients with myeloid malignancies.

These methods of sample collection are non-invasive, amenable to in home collection, and are temperature stable. Collection of saliva and nails could be easily utilized for remotely administered studies by mailing collection kits to participants, thus avoiding the cost and labor of a blood draw.

There was an inverse relationship between cost/workflow time and analytical performance of assays. The analytical assessments results across the 3 platforms were comparable for inter-run reproducibility, LOD, accuracy, and specificity. Areas of differentiation among the assays included sensitivity and intra-patient concordance, with VariantPlex showing the highest values for each.

In our cohort, we confirmed the association between clinical response to ONV-DAC and SF mutations. These analyses support further investigation of the ONV-DAC combination in R/R AML patients with SF mutations and the potential use of ONV-DAC for other hematological diseases with high prevalence of SF mutations such as myelodysplastic syndrome and chronic myelomonocytic leukemia.

Pts with higher-risk MDS treated with Ven + Aza had rapid, durable responses and high remission rates. Pts across key mutational profiles achieved meaningful clinical and molecular responses, supporting an all-comers approach. Updated data will be presented, which will provide more follow up time and durability of responses among mutational subsets.

Familial myeloid predisposition syndromes may be suspected following somatic NGS testing, however our data shows that the rate of confirmatory germline testing is low. This has implications for stem cell donor selection and cascade screening of relatives. For genes that are rarely somatically mutated in MDS/AML such as DDX41 and ANKRD26, the likelihood of germline transmission is high and clinical vigilance is essential to ensure timely confirmatory sequencing.