Growth Fraction of Myelocytes In Normal Human Granulopoiesis

Abstract

Abstract. The labelling index (LI) of myelocytes (M) after flash labelling of normal human bone marrow cells with [3H]‐thymidine ([3H]TdR) is always lower that the LI obtained for myeloblasts (MB) and for promyelocytes (PM). This fact can be interpreted in two ways: it may mean that the duration of the G1 phase of the cell cycle is longer in M than in MB or PM, or it may mean that the proportion of cells in cycle, i.e., the growth fraction (GF), is lower in the M population than in MB or PM. the evolution of the LI and of the mean number of grains per cell was monitored in [3H]TdR‐labelled normal bone marrow during in vitro incubation for 50 hr. the generation time, measured by the halving time of the mean number of grains per cell after flash labelling, was similar for M to that for MB and PM. During continuous labelling, the LI of MB and PM reached 1 and the LI value for M never rose to more than 50% of the values recorded for MB and PM after 30 hr. These findings give support to the second hypothesis, i.e., a lower GF in the M population. Good correlation was found between the LI of M and the proportion of mature polymorphonuclear cells in the bone marrow of normal subjects and of patients with chronic benign neutropenia or hyperleucocytosis. Variations in the M growth fraction could be a medium‐term (2‐3 days) regulatory factor in granulocyte production.

Human lymphoid-neutrophil/monocyte restriction co-ordinately activates increased proliferation despite parallel heterogeneity in transcriptional changes

“…Successive increases in the proliferative activity of hematopoietic cell progenitor populations as they undergo separated erythro-myeloid differentiation processes is well documented [35][36][37] . However, if and when a similar change might begin in cells undergoing lympho-myeloid differentiation is unknown.…”

The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination

“…This vision is supported by the finding that only transplantation of (ST)-HSC and MPP's lead to an appreciable repopulation of mature neutrophils in sub-lethally irradiated mice 16 . GMP's have been shown to divide extensively at the population level in both mice and humans using DNA labeling, mitotic indexes, Ki67 and the Fucci reporter 15,[28][29][30] However, all these methods provide snapshots of division at the population level, and do not give insight into the number of amplification divisions that GMP undergo before differentiating into pro-myelocytes.…”

“… 16 GMPs have been shown to divide extensively at the population level in mice and humans using DNA labeling, mitotic indexes, Ki67, and the Fucci reporter. 15 , 28 , 29 , 30 However, all of these methods provide snapshots of division at the population level and do not give insight into the number of amplification divisions that GMPs undergo before differentiating into promyelocytes. Intriguingly, the generation times of these committed progenitors seem very short because ∼50% of the cells already become BrdU/EdU + within 1 to 2 hours of staining, which opens up the question whether this technique produces artificial results.…”

“… 24 During the maturation step of GMPs into neutrophil progenitors, the proliferation capacity of these cells remains under debate, because reported mitotic and/or proliferation indices of promyelocytes and myelocytes vary markedly between studies. 15 , 28 , 29 , 30 In marked contrast to the GMP compartment, which contains few nonproliferative cells, 25 it has been postulated that the (pro)myelocyte pool contains 30% to 50% nonproliferating cells; this can be explained by a relatively long G1 phase or the presence of resting cells. 28 Although not confirmed by other studies, such a “lazy pool” could be an attractive solution to quickly mobilize extra neutrophils upon high demand.…”

“…The GMP in turn can mature into neutrophil specific pro-myelocytes/pre-neutrophils (preNeus 24 ). During the maturation step of GMP's into neutrophil progenitors, the proliferation capacity of these cells remains under debate, as reported mitotic and/or proliferation indices of pro-myelocytes and myelocytes vary markedly between studies 15,[28][29][30] . In marked contrast to the GMP compartment that hardly contains nonproliferative cells 25 , it has been postulated that the (pro-)myelocyte pool contains 30-50% nonproliferating cells, which can be explained by both a relatively long G1 phase or the presence of resting cells 28 .…”