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Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B lymphoblastic leukemia

Overview of attention for article published in Experimental Hematology, May 2016
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#6 of 507)
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

Mentioned by

twitter
45 tweeters

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21 Mendeley
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Title
Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B lymphoblastic leukemia
Published in
Experimental Hematology, May 2016
DOI 10.1016/j.exphem.2016.04.011
Pubmed ID
Authors

Malachi Griffith, Obi L. Griffith, Kilannin Krysiak, Zachary L. Skidmore, Matthew J. Christopher, Jeffery M. Klco, Avinash Ramu, Tamara L. Lamprecht, Alex H. Wagner, Katie M. Campbell, Robert Lesurf, Jasreet Hundal, Jin Zhang, Nicholas C. Spies, Benjamin J. Ainscough, David E. Larson, Sharon E. Heath, Catrina Fronick, Shelly O'Laughlin, Robert Fulton, Vincent Magrini, Sean McGrath, Scott M. Smith, Christopher A. Miller, Christopher A. Maher, Jacqueline E. Payton, Jason R. Walker, James M. Eldred, Matthew J. Walter, Daniel C. Link, Timothy A. Graubert, Peter Westervelt, Shashikant Kulkarni, John F. DiPersio, Elaine R. Mardis, Richard K. Wilson, Timothy J. Ley, Griffith, Malachi, Griffith, Obi L, Krysiak, Kilannin, Skidmore, Zachary L, Christopher, Matthew J, Klco, Jeffery M, Ramu, Avinash, Lamprecht, Tamara L, Wagner, Alex H, Campbell, Katie M, Lesurf, Robert, Hundal, Jasreet, Zhang, Jin, Spies, Nicholas C, Ainscough, Benjamin J, Larson, David E, Heath, Sharon E, Fronick, Catrina, O'Laughlin, Shelly, Fulton, Robert, Magrini, Vincent, McGrath, Sean, Smith, Scott M, Miller, Christopher A, Maher, Christopher A, Payton, Jacqueline E, Walker, Jason R, Eldred, James M, Walter, Matthew J, Link, Daniel C, Graubert, Timothy A, Westervelt, Peter, Kulkarni, Shashikant, DiPersio, John F, Mardis, Elaine R, Wilson, Richard K, Ley, Timothy J, Robert S. Fulton

Abstract

The genomic events responsible for the pathogenesis of relapsed adult B lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole genome, exome, custom capture, RNA-seq, and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. While the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched unrelated donor stem cell transplant. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate novel therapeutic interventions that could alter patient outcomes.

Twitter Demographics

The data shown below were collected from the profiles of 45 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 5%
Unknown 20 95%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 43%
Researcher 6 29%
Professor > Associate Professor 1 5%
Professor 1 5%
Lecturer 1 5%
Other 3 14%
Readers by discipline Count As %
Medicine and Dentistry 8 38%
Agricultural and Biological Sciences 7 33%
Veterinary Science and Veterinary Medicine 2 10%
Biochemistry, Genetics and Molecular Biology 2 10%
Unspecified 1 5%
Other 1 5%

Attention Score in Context

This research output has an Altmetric Attention Score of 30. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 September 2017.
All research outputs
#331,277
of 8,714,040 outputs
Outputs from Experimental Hematology
#6
of 507 outputs
Outputs of similar age
#17,067
of 274,850 outputs
Outputs of similar age from Experimental Hematology
#1
of 33 outputs
Altmetric has tracked 8,714,040 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 507 research outputs from this source. They receive a mean Attention Score of 2.8. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 274,850 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.