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Expedited Assay and Analysis to Determine Acute Myeloid Leukemia Patient Prognosis

An inexpensive high-throughput clinical diagnostic method for assessing genomic DNA methylation at multiple specific loci coupled with a scoring system allowing for AML prognosis classification. 

 

Problem:

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and affects 12.2 per 100,000 people older than 65 years old. Only 50-80% of patients reach complete remission (CR) as a result of standard chemotherapy while the rest suffer from side effects without significant benefit to their health.

Variable response to chemotherapy in AML represents a major treatment challenge. While clinical and genetic features incompletely predict outcome, there is a clear correlations between patient outcome in AML and DNA methylation patterns. However, tests directly measuring multiple-locus DNA methylation are expensive and technically challenging.

There is a need for a better, cheaper, and readily available diagnostic test to inform clinicians about appropriate treatment and better identify AML patients who are likely to achieve remission.

 

Solution:

 Dr. Carroll and Dr. Wertheim have developed a strategy, multi-locus microsphere HpaII tiny fragment enrichment by ligation-mediated PCR (xMELP), to simultaneously analyze the DNA methylation pattern at up to 50 loci.

This technique is inexpensive and easily performed in a clinical molecular pathology laboratory. Inventors used xMELP to analyze methylation pattern at 18 loci in AML patients and determined methylation statistic (M-score) for 166 patients with de novo AML and in independent cohort of 383 patients from the Eastern Cooperative Oncology Group (ECOG).

M Score segregates AML patients into prognostic subgroups with significantly distinct mortality risk (P = 0.009). In the ECOG study, M-score was associated with death (P = 0.011) and failure to achieve CR (P = 0.034). Median survival was 26.6 months versus 10.6 months for low and high M-score groups. Thus, the xMELP assay and associated M-score can be used for prognosis and for clinical decision making in AML patients. 

 

Inventor: 

Martin Carroll, MD, Gerald Wertheim, PhD, MD

 

 

 

Advantages:  

  • Quantifiable
  • Inexpensive and simple (2 reaction tubes needed)
  • Fast (2 days)
  • Utilizes standard clinical lab equipment

 

Applications:

  • Simultaneous analysis of DNA methylation at up to 50 loci
  • AML mortality prognosis to inform clinicians on appropriate treatments
  • Method can be applied for development of prognostic test for cancers with demonstrated correlation between DNA methylation and clinical prognosis  (T-cell and B-cell lymphoblastic leukemia, NSCLC, ovarian carcinoma, melanoma etc)

 

Stage of Development:

  • Developed xMELP assay and random forest classifier with a training set of an AML patient cohort
  • Validated in three cohorts of patients from UPENN, ECOG and MD Anderson.

 

Reference Media:

Desired Partnerships:  

  • License
  • Co-development

Docket #  15-7238

 

Download PDF

 


Patent Information:
For Information, Contact:
Linara Axanova
Associate Director, PSOM Licensing Group
University of Pennsylvania
axanova@upenn.edu
Inventors:
Martin Carroll
Gerald Wertheim
Keywords: