Triple-negative myeloproliferative neoplasms (TN-MPN): A meta-analysis of clinical and molecular characteristics
Abstract
Triple-negative myeloproliferative neoplasms (TN-MPN), defined by the absence of canonical driver mutations in JAK2, CALR, and MPL, are a biologically heterogeneous subset of BCR-ABL1-negative MPNs. The disease is not well characterized due to rarity of the disease. Non-canonical mutations in TN-MPNs, including rare variants in JAK2, CALR, or MPL not covered by standard assays, as well as somatic alterations in epigenetic regulators and spliceosome components, have been identified in over 50% of cases. A distinct subset of TN-MPN patients, referred to as truly triple-negative (TTN-MPN), lack any mutation, raising the possibility of alternative pathogenicity. The clinical relevance of these molecular subgroups remains underexplored. We conducted a meta-analysis to comprehensively evaluate the clinical, molecular, and thrombotic features of TN-MPNs, with an exploratory sub-analysis comparing TTN-MPNs, mutated TN-MPNs, and driver-mutated MPNs.A literature search was conducted of PubMed, EMBASE and Scopus (updated July 2025) involving observational studies of TN-MPN cohorts with available clinical or molecular data. Eligible studies included ≥2 TN-MPN patients and reported distinct clinical characteristics, thrombotic outcomes or mutation data beyond driver mutations. Results from the literature search were independently reviewed by two authors. Subgroup analysis was performed evaluating patients from Karmanos Cancer Institute, UT Southwestern, Wisconsin School of Medicine and…
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