Retrospective RNA Sequencing Reclassifies a Historical t(5;12) Eosinophilic Neoplasm From Presumed PDGFRB Rearrangement to ETV6::ACSL6.
Frédéric Lambert, Rafael Fernandez Carazo, Benjamin Koopmansch et al.
✦ AI-curated · Sources linked
Case in brief
A woman with a chronic eosinophilic myeloid neoplasm had a t(5;12) that raised suspicion of PDGFRB involvement, but contemporary testing did not identify a rearrangement and empiric imatinib produced no meaningful hematologic response. Seventeen years later, blast transformation occurred with persistence of t(5;12) and acquisition of del(9)(q22). FISH showed ETV6 rearrangement without a PDGFRB break-apart pattern. RNA sequencing of archived blood cells then identified an ETV6::ACSL6 fusion, refining the interpretation of the historical rearrangement.
What made this case unusual
The t(5;12) cytogenetic finding suggested PDGFRB involvement, but RNA sequencing of archived material identified ETV6::ACSL6; FISH indicated en bloc translocation of the PDGFRB locus. The case also documented an unusually prolonged natural history before blast transformation.
Diagnostic / clinical pearl
A t(5;12) breakpoint pattern may not establish the fusion partner. When cytogenetics and clinical response do not support presumed PDGFRB involvement, RNA-based fusion testing of archived material can clarify the rearrangement.
Why it matters
Identifying ETV6::ACSL6 shifted the proposed biological interpretation from constitutive tyrosine kinase activation toward cytokine regulatory rewiring, helping refine expectations about the significance of the rearrangement.