JAK2 Fusions in Adult Patients With Mycosis Fungoides and CD30 Lymphoproliferative Disorders

Janus kinase 2 (JAK2) gene fusions characterize cytotoxic cutaneous T-cell lymphoma (CTCL) including primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL). The identification of these fusions is rarely reported in indolent CTCL.

To characterize patients with CTCL to better understand the diagnostic, prognostic, and therapeutic significance of this molecular alteration in CTCL.

A retrospective case series of patients with CTCL with JAK2 fusions identified between the years 2000 and 2025. Fusions were identified by a custom RNA sequencing panel and by a targeted hybrid-capture-based next-generation DNA sequencing-based panel. The study included a single referral cancer center in the US.

Overall, 43 patients (12 female [27.9%] and 31 male individuals [72.1%]; median [range] age, 45 [16-65] years) with CTCL who were found to have JAK2 gene fusions during evaluation and follow-up were included. Thirty-eight of the 43 identified patients (88.4%) with fusions of JAK2 and 10 different gene partners (most frequently ATXN2L, CAPRIN1, and PCM1) had mycosis fungoides (MF), CD30-positive lymphoproliferative disorders (LPD), or overlap presentations, whereas 4 pcAETCL and 1 peripheral T-cell lymphoma not otherwise specified were identified. Secondary genetic events included mutations of epigenetic and transcriptional regulators. Neither mutational burden, type, or fusion partner distinguished cases with early-stage or aggressive CTCL.

This case series found that JAK2 fusions were seen in aggressive cytotoxic CTCL as well as in T-cell lymphomas with more indolent behavior, possibly representing a precursor lesion to aggressive evolution with age and comorbidities. The prominence of these fusions supports a potentially larger role for JAK2 targeting in patients with early-stage MF, CD30-positive LPD, or overlap presentations.