Circulating hematopoietic progenitor cells in essential thrombocythemia versus prefibrotic/early primary myelofibrosis
Authors: Klaus Geissler, Eva Jäger, Bettina Gisslinger, Juergen Thiele, Ilse Schwarzinger, Heinz Gisslinger
Journal: American Journal of Hematology (2014)

Prefibrotic/early primary myelofibrosis (prePMF) has been clearly distinguished from essential thrombocythemia (ET) with regard to differences in morphology associated with corresponding clinical data 1-3. One of the major characteristics in myeloproliferative neoplasms is quantitative and qualitative changes of the progenitor cell (PC) compartment. Up to now prePMF and ET have not been compared with regard to circulating hematopoietic PCs. Therefore, we compared peripheral PC numbers in ET versus prePMF which are routinely determined at our institution. Between February 1988 and April 2012, PC numbers were determined in 111 patients with ET or prePMF using in vitro cultures assessing CFU-GM and BFU-E growth as previously described 4. Polycythemia Vera Study Group 5 criteria were used before 2002 and the WHO criteria for diagnoses made thereafter. Eligibility criteria included the availability of representative, treatment-naïve bone marrow (BM) biopsies obtained at diagnosis. All BM biopsies subsequently underwent a central re-review (by J.T.) according to WHO criteria 2. The review process was completely blinded to PC data. No patient included in this study was treated by cytoreductive therapy at the time PC determination. The median number of circulating CFU-GM was 364/ml in the ET patients and 802/ml in the prePMF patients. The PB CFU-GM numbers in prePMF were significantly higher as compared to CFU-GM numbers in ET (Fig. 1a). Eleven of seventy-five (15%) patients in the ET group and 16/36 (44%) patients in the prePMF group had CFU-GM values above our range of normal controls (50–936/ml). The median number of circulating BFU-E was 1,325/ml in the ET patients and 1,576/ml in the prePMF patients. The PB BFU-E numbers in prePMF patients were also significantly higher as compared to BFU-E numbers in ET (Fig. 1a). Twenty-two of seventy-five (29%) patients in the ET group and 14/36 (39%) patients in the prePMF group had BFU-E values above our range of normal controls (120–1,862/ml). (a) Comparison of peripheral blood CFU-GM and BFU-E in patients with essential thrombocythemia (ET) and patients with prefibrotic/early primary myelofibrosis (prePMF). Data are shown as boxplots with median values, first and third quartiles, and minimum and maximum values, respectively. (b) Changes of CFU-GM in peripheral blood of two patients with ET and two patients with prePMF over time. In patients in whom PC data at different time points were available, the changes in the PC data over time could be compared in patients with ET and with prePMF. The changes in the CFU-GM numbers could be followed in two prePMF patients and two ET patients. As shown in Fig. 1b, the PC compartment is rapidly expanding in prePMF patients but more or less constant over time in ET. In more than half of our patients, unstimulated in vitro cultures have been performed in addition to stimulated cultures. Not unexpectedly in a substantial proportion of patients, spontaneous growth of erythroid colonies could be observed in unstimulated cultures without exogenous erythropoietin substitution. Endogenous erythroid colony formation was found in 14/44 (32%) of ET patients and in 13/31 (44%) of prePMF patients. Interestingly in 4/31 (13%) patients with prePMF, autonomous CFU-GM formation was observed, whereas it was not detectable in any patient with ET (0/44, 0%). This difference was statistically significant by the chi-squared test (P = 0.021). In conclusion, our results show distinct differences in the hematopoietic PC compartment between ET and prePMF which further suggest differences in biology. Klaus Geissler,1,2* Eva Jäger,3 Bettina Gisslinger,4 Juergen Thiele,5Ilse Schwarzinger,3 and Heinz Gisslinger4 15th Department of Internal Medicine-Oncology/Hematology, Hospital Hietzing, Vienna, Austria; 2Ludwig Boltzmann Institute for Clinical Oncology, Vienna, Austria; 3Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; 5Institute of Pathology, University of Cologne, Cologne, Germany