Next Generation Sequencing
Support and Educational Content

Next generation sequencing for risk assessment in acute myeloid leukemia

xGen® AML Cancer Panel v1.0 provides increased coverage of over 260 AML genes in 71 cases

Klco J, Miller C, et al. (2015) Association between mutation clearance after induction therapy and outcomes in acute myeloid leukemia.. JAMA 314(8): 811–822.

Background

Acute myeloid leukemia (AML) is a cancer of the blood and/or bone marrow. The disease is initially treated with chemotherapy, and recent evidence has shown that aggressive stem cell transplantation can be effective in preventing disease relapse. Transplantation therapies are expensive and not always needed, however, and can have profound side effects. Therefore, a method for determining risk of relapse after chemotherapy would help clinicians in providing this costly treatment only to patients who will benefit from it.

In this paper, the authors use next generation sequencing (NGS) techniques on patients diagnosed with AML to identify associations between specific mutations and disease outcome. They also use these techniques to track the elimination of leukemia-specific mutations in AML patients following chemotherapy.

Experiment

Klco and colleagues first collected bone marrow samples from 71 subjects at the time of their AML diagnosis. The scientists tracked the outcomes of these patients and split them into 3 groups: those who relapsed within 6 months, those who relapsed between 6 and 12 months, and those who remained in remission for over 12 months. They performed whole-genome or whole-exome sequencing on the 71 samples, and compared the number of common AML mutations between the 3 groups, as well as the amount of total genomic mutation. The IDT xGen® AML Cancer Panel v1.0 was used to target and capture 264 commonly mutated genes in AML. Using this panel, the researchers were able to increase depth of coverage from 119X to 215X.

The researchers then sequenced bone marrow samples from 50 patients, including 25 subjects from the previous 71, and 25 new subjects, using the xGen AML Cancer Panel or an exome capture panel supplemented with the xGen AML Cancer Panel. In these 50 patients, they identified leukemia-associated mutations at diagnosis and monitored the mutations’ elimination or persistence 30 days after induction chemotherapy.

Results

In the first study, the researchers did not observe a significant association between specific AML mutations or total genomic coding mutations and the probability of AML relapse. While the results do not provide a method to improve the assessment of patient outcome, they do shed light on the genetic complexity of the disease.

In the second study, the researchers found that 24 of 50 patients had persistent leukemia-associated mutations in their bone marrow cells after chemotherapy. These patients had a significantly increased likelihood of relapse and reduced overall survival (median 10.5 months) compared to those with successful mutation elimination (median 42.2 months). The results of this second study demonstrate the important role that genetic mutation plays in AML and also suggest that targeted NGS techniques can improve risk assessment of patients with AML.

Product focus: Target capture reagents from IDT


xGen® Lockdown® Probes

xGen Lockdown Probes are individually synthesized, quality controlled, and normalized hybridization probes that offer:

  • Sensitive detection of SNPs, indels, CNV, LOH, and translocations
  • GMP compliance for clinical and diagnostics research
  • Flexibility to augment existing panels or create completely custom panels
  • Quick delivery

Discover more about xGen Lockdown Probes.


xGen® Lockdown® Panels

xGen Lockdown Panels are preconfigured, validated, and stocked pools of xGen Lockdown Probes for targeted next generation sequencing of defined gene families:

  • xGen Exome Research Panel 
  • xGen Acute Myeloid Leukemia (AML) Panel
  • xGen Pan-Cancer Panel
  • xGen Inherited Diseases Panel

Discover more about xGen Lockdown Panels.


xGen® Blocking Oligos

xGen Universal Blocking Oligos for single- or dual-index adapters used with common sequencing platforms improve on-target performance for multiplexed samples by reducing adapter participation in hybridization enrichment. Custom adapters can be manufactured for other barcodes or to meet the needs of customers who require specific modifications or services to improve performance in unique applications.

Discover more about xGen Blocking Oligos.

Additional reading

  • Citation: Gene panels vs. gene by gene analysis for assessing disease risk—A comparison of NGS-based gene panel and traditional testing data for diagnostic use and disease risk assessment in hereditary breast and ovarian cancer. xGen Lockdown Probes (IDT) were used to rescue drop-out regions of SureSelect (Agilent) probe panels.
  • Product spotlight: Get the most out of your NGS samples—expandable tumor and disease target capture panels—Learn about expandable NGS target capture panels that enrich for mutated genes implicated in tumors and genes associated with inherited diseases. Designed in collaboration with experts from the Emory Genetics Laboratory and the Cancer Genome Atlas, both panels return consistent results with high reproducibility and deep uniform coverage. 
  • ArticleGet the most out of your NGS samples—Expandable NGS target capture panels that enrich for mutated genes implicated in tumors and genes associated with inherited diseases. Both panels return consistent results with high reproducibility and deep uniform coverage.


Review other DECODED Online newsletter articles on NGS applications.

You can also browse our DECODED Online newsletter for additional application reviews, lab tips, and citation summaries to facilitate your research.


Author: Nolan Speicher is a scientific writing intern at IDT.

© 2015 Integrated DNA Technologies. All rights reserved. Trademarks contained herein are the property of Integrated DNA Technologies, Inc. or their respective owners. For specific trademark and licensing information, see www.idtdna.com/trademarks.


xGen® Blocking Oligos

Adapter blocking oligos increase the number of on-target reads by preventing non-specific binding during hybridization.

Find blockers for your platform ≫


Related Articles

Target Enrichment Facilitates Focused Next Generation Sequencing

The rationale and benefits of enriching subsets of the genome (target enrichment by hybrid capture) prior to sequencing.

Read more ≫

Improving Uniform Coverage of Targeted Sequences for NGS

The challenges faced in obtaining uniform coverage of NGS data and how IDT xGen® Lockdown® Probes are uniquely positioned to facilitate uniform sequence coverage.

Read more ≫

Towards Providing Personalized Medicine—Considerations for Reliable NGS Data

Geneseeq Technology, Inc. demonstrates how they improved their target capture methods to increase accuracy in clinical diagnostics by using optimized blocking oligos and stringent hybridization conditions.

Read more ≫

Delivering Comprehensive Genomic Profiling for Clinical Cancer Care Using Targeted Sequencing

Read how scientists at Foundation Medicine, Inc use hybrid selection in their FoundationOne® Test to help clinicians select patient specific treatment options.

Read more ≫

Insertion Site Detection and Targeted RNA Capture Using Next Generation Sequencing

Scientists at Cofactor Genomics use in-solution hybridization to focus on regions of interest for next generation sequencing.

Read more ≫