Characterization of circulating progenitors in patients with myelofibrosis: clonal origin of progenitor cells and prevalence of colony forming unit-megacaryocyte

Circulating hemopoietic progenitors are usually detected in the peripheral blood of patients with Myelofibrosis with Myeloid Metaplasia (MMM) but quantitative and qualitative aspects are poorly understood. We thus studied 18 patients with primary MMM: circulating CD34+ cells and functional assays of early and committed hemopoietic progenitors [LTCIC,CFC,Colony Forming Unit-Megacaryocyte (CFU-Mk) and Fibroblast-CFU (CFU-F)] were carried out, as well as cytogenetics and clonality on fresh peripheral blood MNC and on progenitors. The results are shown in the table. Circulating CD34+cells/microL were 198 (0-2863).Circulating CFU-Mk and CFU-F were found in the peripheral blood (PB) of MMM patients and not in other myeloproliferative diseases (data not shown). Karyotype abnormalities (KA) were present in 4 out of 18 patients; their frequency on fresh cells was: 100%,100%,100%, and 80%;on progenitor cells was:50%,100%,40%, and 10% respectively. KA were also present at LTC-IC level. However, progenitors cells from female patients without cytogenetic abnormalities were shown to be clonal. In conclusion, we show here that: 1 )the PB of MMM patients contains putative stem cells (LTC-IC) which seem to be involved in the disease; 2)circulating megakariocyte progenitors are constantly present in considerable numbers in the blood and circulating CFU-F are found in about 30% of patients. These findings seem to be a peculiar feature of MMM. 3)Combined data of cytogenetics and clonality seem to exclude persistence of normal residual hemopoiesis. These findings would restrict the perspectives of autografting in MMM. However, further studies are needed to evaluate whether some normal progenitors are still present in PB of MMM patients. CFU-GM BFU-E CFU-GEMM CFU-Mk CFU-F LTC-IC N. Pts 18/18 8/18 4/18 10/10 4/14 12/17 Median /10E5 43 0 0 168 0 5 Range 5-200 0-65 0-12 3-355 0-44 0-111 mL(10E3) 3.66 0 0 10.08 0 0.01 Range (10E3) 0.15-26.4 0-3.9 0-0.38 0.27-72.5 0-0.11.