Patients with idiopathic myelofibrosis show increased CD34⁺ cell concentrations in peripheral blood compared to patients with polycythaemia vera and essential thrombocythaemia

Abstract

The aim of the present work was to compare the results for some haematological variables in 12 patients with idiopathic myelofibrosis (IMF) with those of 21 patients with polycythaemia vera (PV), 22 patients with essential thrombocythaemia (ET) and 10 healthy control subjects. In each patient and control subject peripheral blood was used for analysis of flow cytometric measurement of CD34-positive (CD34+) cells, in vitro colony growth and plasma erythropoietin (EPO) concentration. The mean concentration of CD34+ cells in the IMF group was 568 +/- 686 x 10(3) mL, which significantly (P<0.001 for each group) exceeded the means in PV, ET and control groups ((10.2 +/- 32.0) x 10(3) mL, 3.0 +/- 3.7 x 10(3) mL and 1.9 +/- 0.8 x 10(3) mL, respectively). The mean number of EPO-independent erythroid colonies (EEC) was 110 +/- 215 colonies per 10(5) cells for the IMF patients. In comparison with the means for PV and ET patients (40 +/- 140 and 12 +/- 27 colonies per 10(5) cells, respectively) the difference did not reach statistical significance. The mean EEC for IMF patients was, however, significantly higher compared with the mean for the control subjects (P<0.05). The means for total erythroid colony growth with EPO added to the growth medium as well as for granulocyte-macrophage colony-forming units were significantly higher in the IMF group compared with the means for PV, ET and control groups (P<0.001 for each group). The mean plasma EPO was 204 +/- 290 IU/L in the patients with IMF compared with 6.6 +/- 7.9 IU/L in PV patients, 19.1 +/- 23.2 IU/L in ET and 10.3 +/- 7.8 IU/L in the control subjects. Due to considerable differences in haemoglobin concentrations no relevant conclusions could be drawn from the results for plasma EPO concentrations. Indeed, the majority of patients with IMF, PV and ET were on myelosuppressive treatment; additionally most PV patients received phlebotomy therapy. The results of the present study suggest that the circulating pool of stem cells and progenitor cells in peripheral blood is significantly increased in IMF patients compared with PV and ET patients as well as healthy control subjects. The most likely source for the elevated CD34+ cell concentration in peripheral blood is progenitor cells of extra-medullar origin.

Evaluation of circulating endothelial cells, VEGF and VEGFR2 serum levels in patients with chronic myeloproliferative diseases

“…Although disputing data are present in literature [45], several papers confirm our results [46][47][48]. Apparent differences between these results and other data previously reported could be explained with the heterogeneity of the subjects studied and the stage of disease.…”

Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence

“…(3) The huge mobilization of hematopoietic progenitors from bone marrow to spleen and liver has been documented by an up to 200-fold increase in the circulating CD34 ϩ cell count 42,43 and by their presence in large numbers in the spleen (M.-C.L.B.-K., personal results, August 27, 2008). This regularly observed HSC/HP egress strengthens the hypothesis of an abnormal migration and location of hematopoiesis in anatomic sites other than bone marrow.…”

“…The number of circulating CD34 ϩ cells is considerably elevated in PMF patients compared with other Ph Ϫ chronic myeloproliferative disorders (PV and ET) and is presently considered to be a marker of clinical importance for the diagnosis and the outcome of the disease. 42,43 As the genuine signature of PMF, myelofibrosis results from a complex process including alterations of fibroblasts, leading to a modified expression of adhesion molecules and to an increased deposition of extracellular matrix components. This accumulation is thought to be the consequence of an excessive release/leakage of growth factors within the bone marrow by cells from the pathological hematopoietic clone and especially by necrotic megakaryocytes.…”

Molecular Advances Toward the Understanding of the Patho-Biology of Idiopathic Myelofibrosis

“…In both the mouse models of and in patients with IM, an increase in the number of stem/progenitor cells has been observed in the blood [39,49,[108][109][110][111][112]. In the mouse, cells with the stem cell phenotype capable of forming hematopoietic colonies in semisolid media are detectable in the blood at 8-month of age and their number remains high up to 15-16-month (Fig.…”