Non-invasive multiparametric characterization of essential thrombocythemia, premyelofibrosis, and overt myelofibrosis.
Key claim: Non-invasive inflammatory, immune-activation, and matrix-regulator markers effectively discriminate overt PMF and partially separate prefibrotic MF from ET, supporting a pathophysiological continuum across these MPN subtypes.
Abstract
Among myeloproliferative neoplasms (MPN), prefibrotic myelofibrosis (preMF) was defined as a distinct entity from essential thrombocythemia (ET) and primary overt myelofibrosis (PMF) since the 2016 revision of the World Health Organization (WHO) classification, while precise characterization may be difficult in some instances. In that context, several non-invasive parameters have shown potential to differentiate ET from PMF. The aim of the study was to prospectively evaluate non-invasive parameters in 128 patients (44 ET, 53 preMF, and 21 PMF). The mutational landscape became increasingly complex across diagnostic from ET to preMF and PMF. We observed significant differential expression of inflammatory mediators (IL-1RA, IL-1β, IL-6, S100A8/S100A9, CCL4), immune activation markers (CD25 and CXCL10), matrix regulator (YLK-40 and TIMP1), and lower levels of EGF and CXCL4 between ET and PMF with similar results between preMF and PMF. The two-step Lasso regression strategy to classify patients with internal bootstrap validation reliably identified PMF (AUC: 0.909 [0.804-0.994]) and reasonable discrimination between ET and preMF (AUC: 0.762 [0.656-0.847]). The non-invasive parameters studied enable effective discrimination of PMF and help to distinguish preMF from ET, although the low discriminatory power of these parameters supports the hypothesis of a pathophysiological continuum between these conditions.
Why this matters
Distinguishing ET, prefibrotic MF, and overt PMF currently hinges on bone marrow morphology, with meaningful inter-observer variability and prognostic consequences (e.g., pre-PMF’s worse OS and thrombocytosis penalty vs ET). A validated non-invasive multiparametric signature that cleanly separates overt PMF and partially resolves ET vs preMF would sharpen subtype-specific prognostication and reinforce the emerging view that these entities lie on a single inflammatory-fibrotic continuum rather than being discrete diseases.