Identification of a Novel CSNK2A1-PDGFRB Fusion Gene in a Patient with Myeloid Neoplasm with Eosinophilia

Abstract

Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph‐like ALL

“…Consistent with our findings, some studies have reported that PDGFRB rearrangement leads to increased proliferation and reduced apoptosis of Ba/F3 cells 15,16 . Kathryn G. Roberts et al 23 .…”

“…reported that PDGFRB rearrangement was identified in 1.6% of the 2506 cases with BCR‐ABL1‐like ALL 12 . Up to now, only a minority of fusion partners of PDGFRB, most commonly ETV6‐PDGFRB and EBF1‐PDGFRB, have been recurrently reported, while the vast majority have only been described in case reports 13–17 . PDGFRB rearrangement remains a rare and less‐studied subtype of Ph‐like ALL.…”

“…We evaluated the effects of the TERF2::PDGFRB fusion gene on drug sensitivity in vivo. Mice expressing the TERF2::PDGFRB fusion gene displayed sensitivity to imatinib, resulting in significantly prolonged survival (p < 0.001), with a median survival of 31 (28-) days in BT + IMA mice and 14 (13)(14)(15)(16) days in BT-IMA mice (p < 0.001, Figure 3A). However, after discontinuation of imatinib, peripheral blood GFP levels gradually increased, ultimately leading to the demise of the mice (Figure 3A,E).…”

The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review

“…However, the deletion of CSNK2B , which codes for the CK2β subunit, is present in diffuse large B-cell lymphoma (DLBCL) [ 163 ]. Additionally, a recent case of the CSNK2A1 fusion gene is present in a myeloid neoplasm, indicating the diverse roles of CK2 implications in cancer [ 164 ].…”

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

“…Other gene fusion partners of PDGFRA include the breakpoint cluster region (BCR) ( Yigit et al, 2015 ), KIF5B ( Score et al, 2006 ), the CDK5 regulatory subunit associated protein 2 (CDK5RAP2) ( Walz et al, 2006 ) and the ETS variant transcription factor 6 (ETV6) ( Yoshida et al, 2015 ). As for PDGFRB, approximately 70 fusions have been identified with most fusion partners normally containing an oligomerization motif that mediates dimerization, causing continuous kinase domain activation in myeloid neoplasms ( Campregher et al, 2017 ; Sheng et al, 2017 ; Xu et al, 2020 ). Autocrine PDGFR signaling plays an essential role in cancer progression in ovarian ( Matei et al, 2006 ), breast ( Jechlinger et al, 2006 ), thyroid ( Adewuyi et al, 2018 ), and brain ( Lokker et al, 2002 ) cancers.…”