Proliferative characteristics of Philadelphia-negative myeloproliferative neoplasms - clinical implications

Introduction: Philadelphia-negative myeloproliferative neoplasms (Ph^- MPN) are characterized by overproduction of one or more blood cell lines.

Methods: We studied the proliferative characteristics of 91 patients with de novo Ph^- MPN. Colony-forming cells (CFC) and endogenous colonies (EC), from bone marrow (BM) and/or peripheral blood (PB), were analyzed by colony assay based on methylcellulose. The level of circulating CD34⁺ cells was determined by flow cytometry.

Results: The total number of PB CFC in primary myelofibrosis (PMF) was increased compared to the control sample (P < 0.01) and essential thrombocythemia (ET) (P < 0.05). The highest number of BM and PB EC was observed in polycythemia vera (PV) (P < 0.01). Increased levels of CD34⁺ cells characterized early-prefibrotic (57%) and advanced-fibrotic PMF (90%) as compared to PV (34%) and ET (32%) (P < 0.01). In the whole Ph^- MPN group, the total number of PB CFC (P < 0.01), PB EC (P < 0.05), and CD34⁺ cells (P < 0.01) correlated with the degree of BM fibrosis. Higher levels of circulating CD34⁺ cells in PMF correlated with the total number of PB EC (P < 0.05) and degree of BM fibrosis (P < 0.01).

Conclusions: Exploration of the PB proliferative characteristics of Ph^- MPN on diagnosis may be helpful in revealing early-prefibrotic PMF. Monitoring the levels of circulating CD34⁺ cells may provide a sensitive indicator of fibrotic evolution in PV and PMF.