Blood erythroid progenitors (CFU-E and BFU-E) in acute lymphoblastic leukemias

Abstract

Circulating erythroid progenitors from 14 patients with acute lymphoblastic leukemia (ALL) and from 8 healthy subjects were studied in culture to determine the frequency and size of CFU-E- and BFU-E-derived colonies. Cells were cultured in a plasma clot system, and hemoglobinized colonies identified by diaminobenzidine reaction. The numbers of CFU-E and BFU-E per milliliter of peripheral blood were greatly increased in 10 patients when compared to controls. In 13 patients, the size distribution of BFU-E-derived colonies, analyzed by counting the number of subunits in each colony, was also found to differ significantly from controls, with a large excess of small colonies and a low percentage or a total lack of large colonies. This abnormal BFU-E size distribution was partially corrected, in the 5 patients tested, by the addition to the culture medium of 10% phytohemagglutinin-leukocyte-conditioned medium (PHA-LCM). Bone marrow crowding out of the normal progenitors, as well as disturbances in the cellular interactions involved in their normal development, most likely explain these results and these factors could be implicated in the frequent pancytopenia of ALL.

Increased colony growth in peripheral blood cultures from patients with ALL depends on immunological subtype*

“…We describe a discrepancy between colony growth in bone marrow (BM) and peripheral blood (PB) cultures in patients with newly diagnosed ALL. As observed previously by Chervinsky et al ( l l ) , Praloran et al (12), Geissler et al (13) and Ragab et al (14), we found that colony-forming capacity is lower in BM than in PB. We found, however, that the phenomenon of increased colony growth in PB cultures does not occur in all ALL patients, but depends on the immunological subtype: we did not see it in the immature type, but in ALL with some degree of maturation towards either T ( C D l + and CD4' and/or CD8 + ) or B (CD 10 + ) cells, and only if lymphoblasts were present in the circulation.…”

“…Colony formation in bone marrow cultures from ALL patients is known to be low (5-1 l), probably due to a "dilution" effect of precursor cells with lymphoblasts. On the other hand, colony formation in peripheral blood cultures from ALL patients has been found to be high in some patients (1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It is not known why this phenomenon is not seen in all ALL patients (12,13).…”

Pluripotent and committed haemopoietic progenitor cells in rat peripheral blood

“…In addition to pluripotent progenitors (CFU-S, colony forming units-spleen, 'mature' stem cells or 'pluripotent progenitors'), further investigations demonstrated the existence of primitive pluripotent stem cells (MRA, cell responsible for marrow repopulating ability, i.e. pre-CFU-S) (Lord et al 1995) and committed progenitors in murine and human peripheral blood (Rubin and Cowan 1973;Hara and Ogawa 1977;Praloran et al 1989;Lord et al 1995). The existence of circulating haemopoietic progenitors and stem cells enabled the qualitative advancement in clinical transplantation of haemopoietic stem and progenitor cells; it was possible to mobilise stem and progenitor cells from bone marrow to blood, and to harvest and transplant those cells.…”

“…On the other hand, although the data published for the number of peripheral blood BFU-E in humans, dogs and mice (Table 4) are very heterogeneous, some studies revealed a comparable incidence for human BFU-E (Eridani et al 1984; Biljanovi6-Paunovi6 et al 1990) as we have found here for the rat BFU-E. CFU-E were not detected in the peripheral blood of rats, and the same has been demonstrated for mice (Hara and Ogawa 1977). The incidence of CFU-E in human peripheral blood in a steady state is very low (Praloran et al 1989), if detectable at all. Generally, the incidence of erythroid progenitors in the peripheral blood of rats seems to be low.…”