Characteristics of circulating megakaryocyte progenitors (CFU‐MK) in patients with primary myelofibrosis

Abstract

Characteristics of circulating CFU-MK and the effect of serum and plasma on CFU-MK growth were studied in 14 patients with primary myelofibrosis (MF) using short-and long-term culture methods. The number of CFU-MK in short-term cultures was significantly increased in the non-splenectomized patient group (p < 0.01).Without added PHA-LCM and normal serum, spontaneous colony formation was found in 9 out of 10 patients. In long-term blood cultures from 6 MF patients, 3 untreated patients formed confluent adherent layers and produced in suspension an equal number or an even greater number of nucleated cells, megakaryocytes and CFU-MK than those obtained in long-term bone marrow culture from normal individuals. 2 splenectomized patients showed neither an increased numbers of CFU-MK nor the capacity to develop an adherent layer. The serum and plasma of MF patients failed to stimulate megakaryocyte colony formation by normal bone marrow in a normal fashion. These findings indicate a megakaryocytopoietic abnormality, and a central role of the spleen in extramedullary haematopoiesis in MF.

Serum from patients with various thrombopoietic disorders alters terminal cytoplasmic maturation of human megakaryocytes in vitro

“…Thombocytotic sera (PTS and STS) might be expected to inhibit (platelet products), stimulate, or have no effect on maturation. PTS did not alter cytoplasmic maturation, size or ploidy, which agrees with evidence that primary thrombocytosis is predominantly an abnormality in the progenitors (12,(26)(27)(28)(29)(30). MK-CSA was not elevated, and CFU-MK were not more sensitive to growth factors.…”

“…MK-CSA was not elevated, and CFU-MK were not more sensitive to growth factors. CFU-MK were increased in number, which eventually resulted in more MK and higher platelet counts (21,(26)(27)(28)(29)(30).…”

Trend of circulating CD34+ cells in patients with myelofibrosis: Association with spleen response during ruxolitinib treatment

“…The functional imbalance of the malignant haematopoietic clone in patients with BCR::ABL1 ‐negative MPNs results in an increase in progenitor cells, including pluripotent and committed progenitors, in both the PB and BM 30–34 . Particularly in MF the number of circulating haematopoietic precursors, typically measured by flow cytometry, has always been reported as constantly high, with average levels from eight‐ to 167‐times higher than those found in control subjects.…”

“…The functional imbalance of the malignant haematopoietic clone in patients with BCR::ABL1 ‐negative MPNs results in an increase in progenitor cells, including pluripotent and committed progenitors, in both the PB and BM. 30 , 31 , 32 , 33 , 34 Particularly in MF the number of circulating haematopoietic precursors, typically measured by flow cytometry, has always been reported as constantly high, with average levels from eight‐ to 167‐times higher than those found in control subjects. Consequently, it has been hypothesised that the circulating pool of CD34 + cells in these patients may increase along with the proliferative capacity of the individual disease, and this pool may have the potential to represent the proliferative patterns of such malignancies.…”