Circulating haemopoietic progenitor cells in primary and secondary myelofibrosis: relation to collagen and reticulin fibrosis

Abstract

The relationship between the extent of bone marrow reticulin and collagen fibrosis and the concentration of granulocytic (CFU–GM), erythroid (BFU–E) and megakaryocyte (CFU–Mk) progenitor cells in the peripheral blood of patients with primary agnogenic myeloid metaplasia (AMM) and secondary myelofibrosis (sMF) has not been definitively correlated. We studied 23 patients with established diagnosis of AMM and 12 patients with sMF for the extent of reticulin and collagen bone marrow fibrosis and for the spontaneous colony (sCFU–GM, sBFU–E and sCFU–Mk) formation. The control group consisted of 11 healthy volunteers. Trephine biopsy of the posterior iliac crest was performed in all individuals studied to determine the type and degree of reticulin and collagen fibrosis. Gomori's silver impregnation technique was used. sCFU–GM, sBFU–E and sCFU–Mk colony formation was related positively to spleen size, the white blood cell counts and the degree of collagen fibrosis in AMM (p < 0.01). Stimulated CFU–GM were also significantly correlated with the degree of bone marrow reticulin and collagen fibrosis. There was no correlation between the extent of peripheral blood progenitor concentration and the degree of bone marrow reticulin or collagen fibrosis in sMF and in control individuals. In conclusion, the extent of bone marrow fibrosis is significantly correlated with the peripheral blood progenitor colony formation in AMM but not in sMF.

Proliferative characteristics of Philadelphia‐negative myeloproliferative neoplasms ‐ clinical implications

“…Several previous studies have found increased numbers of pluripotent and committed progenitor cells in the BM and/or PB in Ph − MPN due the functional derangement of the malignant hematopoietic clone and extramedullary hematopoiesis . Our results are generally in concordance with these previous studies, except for the findings regarding proliferative characteristics in ET , where we found a significantly decreased number of total BM CFC, whereas in PV and PMF pts it was almost normal.…”

“…The cultures were incubated in duplicates in a fully humified atmosphere with 5% CO 2 at 37 °C. After 14 days, both endogenous and stimulated colonies were counted in situ based on morphological characteristics under inverted microscope (Zeiss Opton ICM 405, ® Germany) as described by Iscove for BFU‐E and colony‐forming units granulocyte–macrophage CFU‐GM , and by Messner for CFU‐Mk .…”

“…The most specific effect of this mutation is in vitro proliferation of growth factor‐independent colonies of erythroblasts and megakaryocytes, known as endogenous colonies (EC) . This finding has been used as a specific biological marker in differential diagnosis of Ph − MPN as against other reactive conditions . The exact mechanism by which JAK2 mutation causes a pool of hematopoietic stem cells and committed progenitors to differentiate in vitro has not yet been determined .…”

“…In addition to several already known aberrant signaling growth factor pathways, there is also evidence that disturbances of the microenvironment may play a significant role in Ph − MPN pathogenesis . The functional derangement of the malignant Ph − MPN hematopoietic clone results in an increase of pluripotent and committed progenitor cells in BM and peripheral blood (PB) . In contrast to PB, an increased number of BM hematopoietic colonies was not confirmed in all studies performed in Ph − MPN .…”

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.…”