Primary polycythaemia: positive diagnosis using the differential response of primitive and mature erythroid progenitors to erythropoietin, interleukin 3 and alpha‐interferon

Abstract

Forty adult subjects were studied with the aim of establishing positive diagnostic criteria in primary proliferative polycythaemia (polycythaemia vera, PPP). These comprised 14 patients with PPP, eight secondary polycythaemia (SP), five idiopathic erythrocytosis, and 13 normal subjects, classified under standard criteria following comprehensive investigation for causes of SP. Erythroid colony formation from peripheral blood in a serum-free system was assayed with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha-interferon (alpha-IFN). The differential sensitivity of primitive and mature progenitors (BFU-E) was assessed by counting the number of clusters ('sub-colonies') comprising each erythroid burst. 'Endogenous' erythroid colonies were found in both PPP (56%) and controls (17%). In Epo containing cultures, the mean number of clusters per burst was lower in PPP than controls, and the percentage of small (less than or equal to 8 clusters) bursts was higher. In PPP primitive BFU-E demonstrated greater dependence on IL3 than controls, and mature BFU-E greater inhibition by alpha-IFN. These findings suggest an abnormal response to several growth factors, rather than dysfunction of a single growth factor receptor. Regression analysis of these data defined a discriminant of high diagnostic sensitivity and specificity. This discriminant accurately predicted diagnosis in a further nine polycythaemic patients.

The gene encoding hematopoietic cell phosphatase (SHP-1) is structurally and transcriptionally intact in polycythemia vera

“…Puri®ed erythroid progenitors and de®ned serum-free culture conditions have been used to show that erythroid progenitors are hypersensitive to several dierent growth factors (Dai et al, 1992(Dai et al, , 1994Correa et al, 1994;Dudley et al, 1990). Furthermore, granulocyte/monocyte and megakaryocyte progenitors also displayed hypersensitivity to some growth factors (Dai et al, 1992;Kobayashi et al, 1993), a ®nding which accords well with the raised white blood cell and platelet counts often seen in patients with PV.…”

Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis

“…Several studies have provided evidence that EEC is a sensitive indicator for latent or occult forms of MPD associated with SVT (Reid et al, 1982;Valla et al, 1985Valla et al, , 1988De Stefano et al, 1997). Nevertheless, EEC has been reported in healthy controls and isolated cases of reactive erythrocytosis and is not observed in about 50% of patients with well-documented ET (Dudley et al, 1990;Masters et al, 1990). Results obtained in serum-free cultures have demonstrated the need for greater standardization of the assay (Correa et al, 1994), and this standardization is now underway (Dobo et al, 2004).…”

In vitro culture growth of erythroid progenitors and serum erythropoietin assay in the differential diagnosis of polycythaemia

“…Our observations suggested that the EEC assay was only appropriate in untreated or phlebotomytreated PV patients, but was unreliable after myelosuppressive therapy. The EEC assay has been previously studied by others in patients with polycythaemia [12][13][14][15][16][17][18], and most investigators found that EECs were present only in PV patients and not in SP. However, some workers could find small numbers of EECs in normal subjects and even in patients with SP [16][17][18].…”