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Non-invasive multiparametric characterization of essential thrombocythemia, premyelofibrosis, and overt myelofibrosis
Carole Mosnier1,2, Marie-Christine Copin1,3, Isabelle Quintin-Roué4
1Univ Angers, Nantes Université, CHU Angers, Inserm, CNRS, CRCI2NA, F-49000, Angers, France.
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.
Insights
Non-invasive markers can differentiate myeloproliferative neoplasms (MPN). This study identified inflammatory and immune markers to distinguish primary overt myelofibrosis (PMF) from essential thrombocythemia (ET) and prefibrotic myelofibrosis (preMF).
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- The 2016 World Health Organization (WHO) classification defined prefibrotic myelofibrosis (preMF) as distinct from essential thrombocythemia (ET) and primary overt myelofibrosis (PMF).
- Accurate differentiation between these myeloproliferative neoplasms (MPN) can be challenging.
- Non-invasive parameters have shown promise in distinguishing ET from PMF.
Purpose of the Study:
- To prospectively evaluate non-invasive parameters for differentiating ET, preMF, and PMF.
- To assess the diagnostic potential of inflammatory mediators, immune activation markers, and matrix regulators.
Main Methods:
- Prospective evaluation of 128 patients (44 ET, 53 preMF, 21 PMF).
- Analysis of mutational landscape complexity.
- Measurement of differential expression of specific inflammatory mediators, immune markers, and matrix regulators.
- Application of a two-step Lasso regression strategy with internal bootstrap validation.
Main Results:
- Mutational landscape complexity increased from ET to preMF and PMF.
- Significant differences in inflammatory mediators (e.g., IL-6, S100A8/S100A9), immune markers (e.g., CD25, CXCL10), and matrix regulators (e.g., YLK-40, TIMP1) were observed between ET and PMF, and similarly between preMF and PMF.
- The Lasso regression model reliably identified PMF (AUC: 0.909) and showed reasonable discrimination between ET and preMF (AUC: 0.762).
Conclusions:
- Non-invasive parameters effectively discriminate PMF and aid in distinguishing preMF from ET.
- The findings support a pathophysiological continuum between these MPN entities.
- These markers offer potential for improved non-invasive diagnosis of MPN subtypes.
