Cell Proliferation in the ‘Preleukaemic’ Phase of Acute Leukaemia

Abstract

In a 13-year-old patient with acute leukaemia the leukaemic blast cells, the nucleated red cells and the megakaryocytes were studied by cytophotometrie determination of the DNA content and autoradiographic labelling with ³H-TdR invitro. In the preleukaemic phase a striking proliferation defect in the early polychromatic erythroblasts was observed, consisting of an accumulation of cells in G₁ and a decreased proportion of cells in S. In the megakaryocytes low DNA values from 2c-8c as compared to 4c-32c in normal megakaryocytopoiesis, and a decreased number of labelled cells between the ploidy stages was observed, indicating a severely restricted polyploidization capacity. These results suggest that in the preleukaemic stage a basic proliferation defect of acute leukaemic is becoming apparent in the so-called non-leukaemic cell systems, leading to peripheral mono- or pancytopenia.

Some Characteristics of the Proliferative Activity of Erythroblasts in Untreated and Treated Acute Leukaemia

“…A similar proliferation defect has also been observed in preleukaemic acute leukaemia [8] and in other conditions showing ineffective erythropoiesis as thalassaemia [7,12] and congenital dyserythropoietic anaemia type II [6], Therefore ineffective erythropoiesis, showing an accumulation of diploid resting cells in the early polychromatic cell compartment, is regarded as a common patho-physiological mechanism, resting on quite different aetiological factors.…”

Characterization of Ineffective Erythropoiesis in Erythroleukaemia

“…A prolifer ation disturbance similar to that observed in the present study was sug gested in preleukaemia [10] and acute leukaemia [6]. This defect was found to be reversible during complete remission of acute leukaemia [8], No remarkable differences of the proliferation pattern of erythroblasts in preleukaemic condition, acute leukaemia and in acute erythroleukaemia could be established.…”

“…To describe this defect within the erythrocyte precursor compartments, in vivo labelling with tritiated thymidine (3H-TdR) in patients with Di Guglielmo's disease was done [4,5,10]. A continuous decrease of the labelling index from normal or subnormal val ues within the basophilic erythroblasts to always lowered values in the po-1 This investigation was performed within a cooperative study of the 'Süddeutsche Hämoblastosegruppe'.…”

Proliferation of Erythroblasts in Refractory Anaemia

“…This result suggests, that either the presynthetic phase is prolonged or a part of the proliferating erythroblasts do not enter the In studies of erythropoietic cell proliferation with in vivo and in vitro methods in diseases with erythropoietic insufficiency, similar results are obtained. The reports concern /f-thalassaemia [11,16], congenital dy serythropoietic anaemia [10], acute leukaemia [6,13], erythroleukae mia' [5,15], 3 cases of refractory anaemia [7], one case of 'preleukaemia' [12] and sideroblastic anaemia [15]. With exception of the inherited di seases it is a matter of erythropoietic insufficiency in leukaemia with or without hyperplastic erythropoiesis and furthermore diseases, which often represent preleukaemic states.…”