Open AccessChemotherapy Resistance in B-ALL with Cryptic NUP214-ABL1 Is Amenable to Kinase Inhibition and Immunotherapy
Author(s) -
Valentirdi,
Steven L. McAfee,
Paola Dal Cin,
Harrison Tsai,
Philip C. Amrein,
Gabriela Hobbs,
Andrew M. Brunner,
Rupa Narayan,
Jared C. Foster,
Amir T. Fathi,
Hanno Hock
Publication year - 2022
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1093/oncolo/oyab052
Subject(s) - dasatinib , ponatinib , medicine , abl , philadelphia chromosome , fusion gene , fluorescence in situ hybridization , blinatumomab , immunotherapy , cancer research , breakpoint cluster region , chemotherapy , oncology , tyrosine kinase , chromosomal translocation , leukemia , gene , biology , imatinib , lymphoblastic leukemia , genetics , cancer , myeloid leukemia , chromosome , receptor
BCR-ABL1 kinase inhibitors have improved the prognosis of Philadelphia-chromosome-positive (Ph+)-acute lymphoblastic leukemia (ALL). Ph-like (or BCR-ABL1-like) ALL does not express BCR-ABL1 but commonly harbors other genomic alterations of signaling molecules that may be amenable to therapy. Here, we report a case with a NUP214-ABL1 fusion detected at relapse by multiplexed, targeted RNA sequencing. It had escaped conventional molecular work-up at diagnosis, including cytogenetic analysis and fluorescence in situ hybridization for ABL1 rearrangements. The patient had responded poorly to initial multi-agent chemotherapy and inotuzumab immunotherapy at relapse before the fusion was revealed. The addition of dasatinib targeting NUP214-ABL1 to inotuzumab resulted in complete molecular remission, but recurrence occurred rapidly with dasatinib alone. However, deep molecular remission was recaptured with a combination of blinatumomab and ponatinib, so he could proceed to allotransplantation. This case illustrates that next-generation sequencing approaches designed to discover cryptic gene fusions can benefit patients with Ph-like ALL.