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Novel PDGFRB fusions in childhood B- and T-acute lymphoblastic leukemia

Leukemia volume 31, pages 1989–1992 (2017)Cite this article

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Acute lymphoblastic leukemia (ALL) is among the most curable childhood cancers with a 90% overall survival in the good-risk category.1 Though the remission and cure rates among newly diagnosed patients have improved, the prognosis for those with relapsed disease remains poor. Better risk stratification integrating cytogenetics and genomics has enabled improvements in therapy and prediction of relapse. Recently the clinical utility of comprehensive genomic profiling (CGP) has been recognized, in particular, for risk stratification of about 25–30% of childhood ALL patients who do not appear to harbor any of the established chromosomal abnormalities (Supplementary Information).2 By way of illustration, a novel subgroup of BCR-ABL1-like ALL has been described, in which patients lack the BCR-ABL1 fusion but exhibit a gene expression profile similar to that of BCR-ABL1-positive ALL.3 Furthermore, some of these patients have been demonstrated to harbor tyrosine kinase-activating fusion genes, notably including PDGFRB and JAK2 fusions. The EBF1-PDGFRB gene fusion has been well studied and found to be responsive to the ABL1 tyrosine kinase inhibitor (TKI), imatinib mesylate.4, 5, 6 Here, we have identified three novel PDGFRB fusions (PDGFRB fused to each of SATB1, AGGF1 and DOCK2) in children with either precursor B-cell (B-ALL) or T-cell ALL (T-ALL). We report the clinical utility of CGP to characterize these previously undescribed activating fusion genes, in conjunction with childhood B- or T-ALL, and describe responses to TKIs.

All three patients were diagnosed to have ALL and were treated in Memorial Sloan Kettering Cancer Center (New York, NY, USA), Huntsman Cancer Center (Salt Lake City, UT, USA) or University of Alabama Cancer Center (Birmingham, AL, USA). Cytogenetic analysis was performed in the treating facilities and CGP was conducted using the FoundationOne Heme assay, a clinical laboratory improvement amendments-approved, NY-state approved assay on whole mononuclear cells from either bone marrow or peripheral blood; FISH testing was also conducted in two of three patients.7 One patient underwent testing for the following FISH probe(s) and locations (s): ASS1, ABL1 (9q34), BCR (22q11.1), PDGFRB (5q32)—all of which were negative; the second patient was only tested for BCR-ABL1, which was negative. The third patient did not undergo FISH testing prior to CGP. Patients were treated in accordance to individual institutions’ protocols. Approval for this study, including a waiver of informed consent and a Health Insurance Portability and Accountability Act waiver of authorization, was obtained from the Western Institutional Review Board (Protocol No. 20152817).

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Author notes

  1. A M Heilmann and A B Schrock: These authors contributed equally to this work.

Authors and Affiliations

  1. Foundation Medicine Inc., Cambridge, MA, USA

    A M Heilmann, A B Schrock, J He, M Nahas, R Erlich, J Ross, P Stephens, V A Miller, S M Ali, J-A Verglio & T I Mughal

  2. Memorial Sloane Kettering Cancer Center, New York, NY, USA

    K Curran, N Shukla & M S Tallman

  3. University of Alabama, Birmingham, MS, USA

    S Cramer

  4. University of Utah, Salt Lake City, UT, USA

    L Draper & A Verma

  5. Albany College of Medicine, Albany, NY, USA

    J Ross

  6. Tufts University Medical Center, Boston, MA, USA

    T I Mughal

Authors
  1. A M Heilmann
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  2. A B Schrock
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  3. J He
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  10. R Erlich
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  16. M S Tallman
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  17. T I Mughal
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Corresponding author

Correspondence to T I Mughal.

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Competing interests

AMH, ABS, JH, MN, RE, JR, PS, VAM, SMA, JAV and TIM are employees of FMI. All other authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Heilmann, A., Schrock, A., He, J. et al. Novel PDGFRB fusions in childhood B- and T-acute lymphoblastic leukemia. Leukemia 31, 1989–1992 (2017). https://doi.org/10.1038/leu.2017.161

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