Mechanism of extramedullary haematopoiesis in rabbits with saponin-induced myelofibrosis and myeloid metaplasia

Abstract

The saponin-induced myelofibrosis and myeloid metaplasia model in the rabbit was used to study mechanisms of extramedullary haematopoiesis. Haematopoietic progenitor cells, erythroid colony forming units (CFU-E) and burst forming units (BFU-E) were assayed serially in the peripheral blood, spleen and bone marrow after saponin administration, employing the in vitro methylcellulose culture technique. Animals that had undergone splenectomy prior to saponin administration were also studied. The results demonstrated increases of progenitor cells in the blood and spleen and a simultaneous depletion of such cells in marrow after saponin treatment. The results in splenectomized animals were similar to those observed in non-splenectomized animals after saponin administration. The findings indicate that following saponin administration there is a release of CFU-E and BFU-E from bone marrow into periphery and probably deposition in the spleen, and suggest that myeloid metaplasia in myelofibrosis may result from colonization of extramedullary sites originating from the bone marrow.

Endometrial extramedullary haemopoiesis

“…Experimental studies have shown that the increased number of these circulating cells is the result of mobilization of stem cells from the bone marrow. [13][14][15] It has been proposed that tissues colonized by haemopoietic stem cells have the ability to support haemopoietic proliferation and differentiation. l 6 The endometrial EMH described in cases 1, 3, and 4 can be explained by the theory of increased numbers of circulating stem cells.…”

Circulating granulocyte and macrophage progenitor cells in primary and secondary myelofibrosis

“…In our patients, splenomegaly greater than 4 cm below the left costal margin was found in those with PMF but not in SMF. The spleen has been suggested as a major source of circulating CFU-GM in patients with chronic myelogenous leukaemia (Bagby, 1978) and PMF (Koeffler et a!, 1979;Kirshner et al, 1980). The difference in CHI-GM found in PMF and SMF therefore could be due to the degree of splenomegaly found in the former condition.…”

“…one can postulate that there is disruption of the marrow microvascular system releasing stem cells into the circulation and from there to extramedullary organs, most notably the spleen. This mechanism of stem cell release is thought to occur in saponin-treated rabbits who go on to develop a picture similar to PMF (Wang&Tobin, 1978, 1979. 1982: Hoshi&Weiss, 1978.TheadditionalCFU-GMseen in PMF would then be the probable consequence of abnormal clonal proliferation of haematopoietic stem cells colonizing the spleen.…”