ASH 2020 : Cellworks CBM Identifies Genomic Signatures Impacting HOXA Regulation that Determine Response for AML Patients with
myCare-021-04 study finds genetic signatures associated with 100% remission rate from AML induction therapy despite presence of Monosomy 7
SOUTH SAN FRANCISCO, Calif., December 7, 2020 -- Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, today announced results from the myCare-021-04 clinical study, in which Cellworks Omics Biology Model (CBM) analysis identified genomic alterations that determine chemotherapy response for patients with (-7) and identified novel genomic signatures of response and resistance. The study revealed that Cellworks CBM classification of patients harboring (-7) by HOXA biomarker analysis could enable personalized treatment plans, thereby avoiding unnecessary drug-related patient risks and reducing treatment costs.
Results from the myCare-021-04 clinical study will be featured as Oral and Poster Abstract #2906 on Monday, December 7, 2020 during the all-virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition and published online at Blood®.
“For AML patients, Monosomy 7 is generally associated with poor response to induction chemotherapy,” said Dr. Michael Castro, MD, oncologist specializing in molecular oncology, precision medicine and immunotherapy of cancer and principal investigator for the myCare-021-04 clinical study. “But not all patients fare poorly, so the ability to identify responders and non-responders remains a high priority. Cellworks Omics Biology Model (CBM) analysis can identify genetic signatures associated with therapy response and non-response for AML patients with Monosomy 7 in advance of treatment, which in turn can inform therapy planning and improve patient outcomes.”
“Monosomy 7 is one of the most common cytogenetic abnormalities in pediatric and adult myeloid malignancies, particularly in adverse-risk AML” said Dr. Scott Howard, MD, MSc, Professor at University of Tennessee Health Science Center. “But this study revealed that Monosomy 7 alone does not confer resistance to chemotherapy. Cellworks CBM analysis identified other genomic alterations that determine chemotherapy response, which can enable a personalized approach to therapy.”
myCare-021-04 Clinical StudyPopulation
For this study, genomic data from 13 consecutive patients with (-7) were analyzed using the Cellworks Omics Biology Model (CBM) to generate patient-specific protein network models. All data was anonymized, de-identified and exempt from IRB review.Methodology
For each model, disease simulations were performed and patients were segregated into HOXA-upregulated and HOXA-downregulated cohorts based on the simulation levels of HOXA5 and HOXA9. Digital drug simulations for induction chemotherapy were accomplished by measuring the impact of drug effect on a cell growth score, a composite of cell proliferation, viability and apoptosis indices. Each patient-specific model was analyzed to identify mechanisms underlying treatment outcomes.Findings
In the study, 54% (7/13) of (-7) patients failed to achieve remission after induction chemotherapy, which highlighted that (-7) alone does not confer resistance to chemotherapy. Cellworks CBM analysis identified other genomic alterations that determine chemotherapy response, including DNA repair deficiency genes, mismatch repair (MMR), and homologous recombination repair (HRR) genes.
Study results show that alterations of chromatin regulation have consequences for transcription factors that regulate expression of DNA repair genes. Under conditions where DNA repair is enhanced, induction chemotherapy was 78% less likely to effect remission in (-7) AML patients undergoing induction chemotherapy. Loss of H3K27 methylation associated with loss of PRC2 function by any means resulted in HOXA-upregulation and upregulation of DNA repair genes induced resistance to induction therapy.
On the other hand, Cellworks CBM analysis identified genetic signatures associated with a 100% remission rate from AML induction therapy despite the presence of (-7). Generation of H3K27me caused by PRC2 activation resulting from numerous mechanisms led to HOXA-downregulation and 100% response to induction therapy.
The study demonstrated that stratification of patients harboring (-7) by HOXA biomarker analysis could inform treatment planning, avoid drug-related adverse events and reduce treatment costs.
About Cellworks Group
Cellworks Group, Inc. is a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology. Using innovative multi-omics modeling, computational biosimulation and Artificial Intelligence heuristics, Cellworks predicts the most efficacious therapies for patients. The Cellworks unique biosimulation platform is a unified representation of biological knowledge curated from heterogeneous datasets and applied to finding cures. Backed by UnitedHealth Group, Sequoia Capital, Agilent and Artiman, Cellworks has the world’s strongest trans-disciplinary team of molecular biologists, cellular pathway modelers and software technologists working toward a common goal – attacking serious diseases to improve the lives of patients. The company is based in South San Francisco, California and has a research and development facility in Bangalore, India. For more information, visit www.cellworks.life and follow us on Twitter @cellworkslife.
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