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PubMed1978

Progenitor cells of erythroblasts: an in vitro investigation of erythropoietin-responsive cells of guinea pig bone marrow.

The experiments were designed to test whether or not erythroblast progenitor cell function could be demonstrated in a morphological cell type designated as "transitional cells." Two cell fractions, were obtained from the bone marrow of normal and polycythemic guinea pigs. One fraction (F1) was enriched in transitional cells and contained few, if any, other cell types which could be considered as candidates for erythropoietin responsive cells (ERC). The other fraction (F2) contained undifferentiated blast cells as well as transitional cells. The effect of human urinary erythropoiesis stimulating factors (ESF) on heme synthesis was compared in these two fractions by measuring 59Fe incorporation into heme. ESF was more effective in stimulating heme synthesis in guinea pig bone marrow cells than homologous sera obtained from anemic or hypoxic animals. The majority of ERC sedimented in F2, but the stimulation index was comparable in the two fractions. It was confirmed by radioautography that the ESF response in F1 was due to the generation of proerythroblasts and basophilic erythroblasts that incorporated 55Fe. The generation of these cells in F1 was dependent on the addition of ESF to the cultures, whereas 55Fe-labeled erythroblasts were recovered from cultured of F2 not supplemented with ESF. ESF induced a proportion of transitional cells to incorporate 55Fe in both F1 and F2. Transitional cells were the only cell type in which heme synthesis was dependent on ESF. in other cells of clearly nonerythroid morphology (mononuclear phagocytes and reticular cells), 55Fe incorporation occurred independent of ESF. Although the fractionation procedure employed is unsuitable for the separation of ERC from bone marrow, it permitted the enrichment of transitional cells, a cell type defined by morphology. Radioautography with 55Fe identified a proportion of these cells as ERC in both F1 and F2 fractions of bone marrow obtained from normal and polycythemic guinea pigs. Although there may be other cell types in F2 capable of responding to ESF, the present studies show that some transitional cells function as progenitors of erythroblasts because they respond to ESF by initiation of heme synthesis and by transformation into the earliest recognizable erythroid cells.

Animals↗
PubMed2006

Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in vivo.

BACKGROUND: Artesunate (ART), an artemisinin antimalarial, is embryolethal and teratogenic in rats, with the most sensitive days being 10 and 11 postcoitum (pc), respectively (Clark et al.: Birth Defects Res B 71:380-394, 2004; White et al.: Birth Defects Res A 70:265, 2004). METHODS: In this study, pregnant rats were administered a single oral dose of 17 mg/kg ART on Days 10-11 pc and conceptuses were evaluated through Day 14 pc. RESULTS: Paling of visceral yolk sacs was observed within 3-6 hr after treatment. Within 24 hr, marked paling and embryonic erythroblast depletion were observed macroscopically, which preceded malformations and embryo death, and persisted through Day 14 pc. Histologically, embryonic erythroblasts were reduced and cells showed signs of necrosis within 24 hr, were maximally depleted by 48 hr, and had partially rebounded within 3-4 days after treatment (Days 13 and 14 pc). Iron accumulation was evident in treated erythroblasts as early as 6 hr after treatment, suggesting impairment of heme synthesis. Heart abnormalities (swollen or collapsed chambers) were observed within 24 hr in approximately 25-60% of embryos and within 48 hr in 100% of embryos, correlating with histologic signs of cardiac myopathy (thinned and underdeveloped heart walls and enlarged chambers). Delays in limb and tail development occurred by Day 13 pc. Embryos were viable through Day 13 pc, but approximately 77% of embryos had died by Day 14 pc, presumably due to hypoxia and/or cardiac abnormalities. CONCLUSIONS: In summary, embryonic erythroblasts are the primary target of ART toxicity in the rat embryo after in vivo treatment, preceding embryolethality and malformations.

Abnormalities, Drug-Induced↗
PubMed1994

Identification of two Rh mRNA isoforms expressed in immature erythroblasts.

Two isoforms of RhPI cDNA encoding an Rh polypeptide, RhPI-alpha and RhPI-beta, were isolated from mRNAs of immature erythroblasts cultured in a selective two-phase liquid culture system for human erythroid progenitors in peripheral blood. The RhPI-alpha and RhPI-beta cDNA clones encoded the hydrophobic membrane polypeptides of 242 and 244 amino acids which were missing in amino acid residues 227 to 383 and 212 to 384 of RhPI polypeptide, respectively. These peptide deletions produce unexpected structural properties resulting in the generation of a new open reading frame with a new stop codon caused by frameshift translations in RhPI-alpha cDNA and in the reverse orientation of topology in RhPI-beta cDNA. Both isoforms are abundantly present in immature erythroblasts, but not in mature erythroblasts. These results indicate that the two Rh-related mRNAs identified are expressed at the immature erythroblast stage on the development of erythroid series.

Amino Acid Sequence↗
PubMed1977

On the yolk sac of the cat. II. Erythropoietic phases, ultrastructure of aging primitive erythroblasts, and blood vessels.

The phase of primitive erythropoiesis in the feline yolk sac lasts from the 14th to the 20th day after malting. The globular nucleated primitive erythroblasts are formed extravascularly to some extent, but they can be clearly distinguished from the endoderm. They do not undergo a denucleation and are still present in the circulating blood on the 45th day. Aging primitive erythroblasts are characterized by a loss of polysomes, by the appearance of long intracytoplasmic electron-lucent channels, and by a nuclear pyknosis which can turn into a karyolysis. Definitive erythropoiesis begins around the 17th day but, even by the 19th day, it is not particularly prominent. It ends around the 45th day. It is almost exclusively intravascular. The distinction of immature primitive erythroblasts from erythroblasts of the definitive series is difficult, because it is based upon only slight differences in the heterochromatinization, in the nuclear-cytoplasmic ratio, and in the organelle content of the cells. In the definitive series, the nuclear divisions follows the law of the rhythmical halving of the nuclear volume. The cells exhibit more clearly identifiable maturation stages here, and the 'checkerboard nucleus' is more distinct. The vascular endothelium is largely attenuated and moderately fenestrated; it lacks a distinct basement membrane. Organelle-rich adventitial cells are found in close apposition.

Aging↗
PubMed1981

Quantitation of globin mRNA in individual human erythroblasts by in situ hybridization.

In situ hybridization of globin mRNA was performed in four human bone marrows using a 3H-cDNA derived from rat globin messenger. Erythroblasts were classified according to nuclear area as well as to morphological appearance after Giemsa staining. Grains over individual erythroblasts and reticulocytes were counted by incident light microphotometry. Reticulocytes from phenyl hydrazine-treated rats served as internal standards in order to allow a comparison of different experiments. The preliminary results from one normal bone marrow, one of stress erythropoiesis and two of aplastic anemia revealed the major content of globin mRNA in the states of basophilic erythroblasts or proerythroblasts. In all cases there was a tendency of decreasing globin mRNA content towards orthochromatic erythroblasts, and even more so, towards reticulocytes. The results show some differences between normal and diseased erythropoiesis which are under study on a larger scale now in order to ascertain their significance.

Anemia, Aplastic↗
PubMed1975

Septate-like junctions in abnormal erythroblasts: cytochemical, ultrastructural and freeze-etch studies.

Ultrastructural studies of the bone marrow of a patient with refractory anemia revealed aberrant erythroblasts with unique cell junctions. Periodic structures linked adjacent processes on the same cell as well as surfaces of neighboring erythroblasts. Inclusions circumscribed by similar complexes were also present in the cytoplasm. The junction appeared in cross sections as two rigidly parallel unit membranes separated by 250-300 A interspace with two regular arrays of facing 70 A particles at intervals of 160-200 A. These intracellular specializations were present between erythroblasts at various stages of maturation and between, mono, bi or multinucleated erythroblasts. Junctions were permeable to lanthanum and many that appeared to be intracellular were demonstrated to be continuous with the extracellular space. The fact that others were not penetrated by lanthanum indicates that detachment of the interdigitating processes from cells of origin could have occurred. In freeze-etched replicas, distribution of membrane particles was random in areas of septate-like junctions, although parallel rows were sometimes observed both on A and B inner hydrophobic faces of the membrane leaflets. Junctional complexes in tissue culture appeared to have been disrupted and were not reestablished; however, inclusions resembling internalized junctions were observed associated with multivesicular bodies. Ineffective erythropoiesis and the resulting refractory anemia appear to be associated with the presence of the described anomalous junctional complexes.

Anemia, Aplastic↗
PubMed2003

Decreased expression of membrane alpha4beta1, alpha5beta1 integrins and transferrin receptor on erythroblasts in splenectomized patients with beta-thalassemia intermedia. Parallel assessment of serum soluble transferrin receptors levels.

Dysfunction of cell membrane is a recognized consequence of the pathogenetic process underlying the beta-thalassemia syndromes and it is reasonable to hypothesize that surface structures crucial for the development of erythroid lineage may also be affected. The study included six adult splenectomized patients with beta-thalassemia intermedia. Expression of alpha4beta1 integrin (CD49d/CD29), alpha5beta1 integrin (CD49e/CD29) and transferrin receptor (CD71) on peripheral blood and bone marrow erythroblasts and on erythroid precursors grown in vitro was studied by flow cytometry and immunocytochemistry. Serum soluble transferrin receptor levels (sCD71) were also measured with enzyme-linked immunosorbent assay. In beta-thalassemic patients, significant reduction of CD49d, CD29 and CD71 expression was found in peripheral blood nucleated red cells, compared to patients presenting with erythroblasts in the circulation because of other diseases. Marrow erythroblasts were also deficient for the same molecules against the erythroblasts in iron deficiency anemia. All molecules tested were greatly diminished on erythroid precursors developed in vitro from the patients' cells. Serum sCD71 levels were much higher in thalassemic patients in comparison to both patients with iron deficiency anemia and healthy individuals. The loss of certain integrins and CD71 from erythroid precursors in beta-thalassemia intermedia could be attributed to a generalized membrane dysfunction, perhaps affecting the integrity of their transmembrane domains. The elevation of serum sCD71 levels may be the result of the increased red cell lineage turnover or, alternatively, may indicate increased shedding from the cells to prevent iron overload. In any case, further molecular study of the membrane components is warranted to provide a better understanding of the pathogenetic process in beta-thalassemia syndromes.

Adult↗
PubMed1997

Origin of the central cells of erythroblastic islands in fetal mouse liver: ultrahistochemical studies of membrane-bound glycoconjugates.

To clarify the origin of the central cells in hepatic erythroblastic islands, glycoconjugates on the surface of cellular constituents in fetal mice liver were ultrahistochemically examined using lectin staining. At 11 days of gestation, the cells derived from mesenchyme in fetal liver, including sinusoidal macrophages, endothelial cells, and erythropoietic cells, bound Griffonia simplicifolia isoagglutinin I-B4 (GS-I-B4), but hepatocytes lacked binding sites for the isolectin. Scavenger macrophages in the hepatic cords at 13 days of gestation and the central cells in the erythroblastic islands at 15 days of gestation also bound GS-I-B4. Hepatocytes, however, exhibited no GS-I-B4 binding site at any gestational day. At 11 days of gestation, none of the cells in fetal liver had binding sites for soybean agglutinin (SBA), but cells derived from mesenchyme acquired these binding sites at 13 days of gestation. The central cells in the erythroblastic islands also bound SBA, but hepatocytes did not bind the lectin at all. The central cells in the erythroblastic islands can be considered to belong to a mesenchymal cell lineage, and primitive sinusoidal macrophages at 11 days of gestation are possible precursors of these central cells.

Animals↗
PubMed1986

Classification of beta-adrenergic subtypes in immature rabbit bone marrow erythroblasts.

The beta-adrenergic receptors of immature rabbit bone marrow erythroid cells (proerythroblasts and basophilic erythroblasts) were identified. [125I]iodocyanopindolol bound to membrane preparations derived from these erythroblasts in a rapid, reversible and saturable manner. Scatchard analysis of binding data revealed a single class of binding sites (Hill coefficient of 0.954) with an apparent equilibrium dissociation constant (Kd) of 8 pM, and a density of binding sites (Bmax) of 1.53 pM/10(6) cells, corresponding to 920 receptors per cell. The binding of [125I]iodocyanopindolol was inhibited stereospecifically by concentrations of (-)-propranolol 2 orders of magnitude lower than by the (+)-isomer. Only L-isoprenaline and L-adrenaline activated the adenylate cyclase of immature rabbit erythroblasts, while L-noradrenaline, a beta 1-adrenergic agonist, was inactive. The order of potency of different agonists for displacement of bound [125I]iodocyanopindolol was: isoprenaline greater than adrenaline greater than noradrenaline with respective EC50 (concentration required for half maximal inhibition of binding) of 7.9 X 10(-7) M, 1.5 X 10(-5) M and 7.9 X 10(-5) M. This agonist potency series did not change with differentiation of rabbit bone marrow erythroblasts. The inhibition of specific [125I]iodocyanopindolol binding to immature cells by beta 1- and beta 2-selective drugs (noradrenaline, practolol, procaterol and butoxamine) resulted in linear Hofstee plots. The inhibition curves obtained with procaterol and butoxamine, with apparent Kd values of 3.1 X 10(-9) M and 4.9 X 10(-9) M, further evidence that the high-affinity binding sites correspond to a homogeneous beta 2-receptor subtype.

Adenylyl Cyclases↗
PubMed1983

Characteristics of the beta-adrenergic adenylate cyclase system of developing rabbit bone-marrow erythroblasts.

After fractionation of rabbit bone marrow into dividing (early) and non-dividing (late) erythroid cells, the adenylate cyclase activity of membrane ghosts was assayed in the presence of guanine nucleotides ((GTP and its analogue p[NH]ppG (guanosine 5'-[beta, gamma-imido]triphosphate))), the beta-adrenergic agonist L-isoprenaline (L-isoproterenol) and the antagonist L-propranolol. Both GTP and p[NH]ppG increased the adenylate cyclase activity of early and late erythroblasts, whereas the stimulating effect of the beta-adrenergic drug L-isoprenaline was limited to the immature dividing bone-marrow cells. The effect of L-isoprenaline was completely inhibited by the antagonist L-propranolol, confirming that the response was due to stimulation of beta-adrenergic receptors on the plasma membrane. The lack of response of non-dividing erythroblasts to beta-adrenergic stimuli is not due to loss of beta-receptors, since both dividing and non-dividing cells bind the selective ligand [125I]iodohydroxybenzylpindolol with almost equal affinities, the apparent dissociation constants, Kd, being 0.91 X 10(-8)M and 1.0 X 10(-8) M respectively. The number of beta-adrenergic receptors per cell was 2-fold higher in the dividing cells. No significant change in binding affinity for GTP and p[NH]ppG during erythroblast development was observed: the dissociation constants of both guanine nucleotides were almost identical with early and late erythroblast membrane preparations [2-3 (X 10(-7) M]. With dividing cells, however, in the presence of L-isoprenaline the dissociation constants of GTP and p[NH]ppG were lower (6 X 10(-8) M). The dose-response curves for isoprenaline competition in binding of [125I]iodohydroxybenzylpindolol by dividing cells showed that the EC50 (effective concentration for half maximum activity) value for isoprenaline was higher in the presence of p[NH]ppG. With non-dividing cells the EC50 value for isoprenaline was equal in the presence and in the absence of p[NH]ppG and similar to that observed with dividing-cell membranes in the presence of the nucleotide. Thus differentiation of rabbit bone-marrow erythroid cells seems to be accompanied by uncoupling of the beta-adrenergic receptors from the adenylate cyclase catalytic protein as well as by a decrease in the number of receptors per cell, but not by changes in the catecholamine and guanine-nucleotide-binding affinities.

Adenylyl Cyclases↗
PubMed2000

Excessive apoptosis of bone marrow erythroblasts in a patient with autoimmune haemolytic anaemia with reticulocytopenia.

We report a patient with autoimmune haemolytic anaemia (AIHA) with reticulocytopenia, who showed excessive apoptosis of erythroblasts. Ultrastructural analysis of bone marrow cells showed that 50% of erythroblasts had characteristic features of apoptosis, which was confirmed by staining with Annexin-V. In addition, in contrast to normal erythroblasts, Ig staining of the entire erythroblast population could be shown. These data show that apoptosis may contribute to the mechanism of reticulocytopenia in AIHA.

Anemia, Hemolytic, Autoimmune↗
PubMed1983

Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts.

The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult beta-like globin gene domains were evaluated in greater than or equal to 90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-wk gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic epsilon chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult beta chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression. These results suggest that modulation of the methylation pattern may represent a key mechanism for regulating expression of human globin genes during embryonic leads to fetal and fetal leads to adult Hb switches in humans. In ontogenic development this mechanism might in turn correlate with a gradual modification of chromatin structure in the non-alpha gene cluster, thus leading to a 5' leads to 3' activation of globin genes in a balanced fashion.

Adult↗
PubMed2003

Erythroblast transformation by FLI-1 depends upon its specific DNA binding and transcriptional activation properties.

FLI-1 is a transcriptional regulator of the ETS family of proteins. Insertional activation at the FLI-1 locus is an early event in F-murine leukemia virus-induced erythroleukemia. Consistent with its essential role in erythroid transformation, enforced expression of FLI-1 in primary erythroblasts strongly impairs the response of these cells to erythropoietin (Epo), a cytokine essential to erythropoiesis. We show here that point mutations in the ETS domain that abolished FLI-1 binding to specific DNA elements (ETS-binding sites) suppressed the ability of FLI-1 to transform erythroblasts. The exchange of the entire ETS domain (DNA binding domain) of FLI-1 for that of PU.1 changed the DNA binding specificity of FLI-1 for that of PU.1 and impaired FLI-1 transforming properties. In contrast, ETS domain swapping mutants that maintained the DNA binding specificity of FLI-1 did not affect the ability of FLI-1 to transform erythroblasts. Deletion and swapping mutants that failed to inhibit the DNA binding activity of FLI-1 but impaired its transcriptional activation properties were also transformation-defective. Taken together, these results show that both the ability of FLI-1 to inhibit Epo-induced differentiation of erythroblasts and to confer enhanced cell survival in the absence of Epo critically depend upon FLI-1 ETS-binding site-dependent transcriptional activation properties.

Animals↗
PubMed2000

Increased fetal erythroblasts in women who subsequently develop pre-eclampsia.

In pregnancies complicated by pre-eclampsia (PET) and/or intrauterine growth restriction (IUGR) there is an increased number of fetal cells in the maternal circulation. The aim of this study was to investigate whether this increase in fetal cells precedes the onset of these pregnancy complications. Doppler ultrasound studies at 24 weeks gestation have shown that increased impedance to flow in the uterine arteries identifies pregnancies with impaired placental perfusion that subsequently develop PET and/or IUGR. We obtained maternal blood from 18 pregnancies with abnormal Doppler results at 22-24 weeks gestation and from 10 normal controls. Fetal erythroblasts were enriched from maternal blood by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody, and the percentage of these erythroblasts was determined. The median proportion of fetal erythroblasts in the group with abnormal Doppler results was 4.5% (range 1-12%), which was significantly higher than in the control group [median 1% (range 0-3%; P < 0.001)]. Furthermore, within the group with abnormal Doppler the median proportion of fetal erythroblasts was higher in the 10 cases which subsequently developed PET and/or IUGR [median 5.5% (range 3-12%)], than in those with normal pregnancy outcome [median 2% (range 1-5%; P < 0.01)]. These findings suggest that impaired placental perfusion is associated with an increase in feto-maternal cell traffic, which precedes the onset of PET and/or IUGR by several weeks.

Adult↗
PubMed2003

Distribution of fetal erythroblasts enriched from maternal blood in multifetal pregnancies.

BACKGROUND: The aim of this study was to establish the frequency of fetal cells in the maternal blood of multifetal pregnancies and compare this figure with singleton pregnancies. METHODS: We obtained maternal blood from 31 pregnancies with 2-6 fetuses at 11-16 weeks gestation and from 50 normal singleton controls (11-14 weeks gestation). Fetal erythroblasts were isolated from maternal blood using triple density gradient separation and anti-CD71 magnetic cell-sorting techniques. The enriched erythroblasts were stained with Kleihauer-Giemsa and with fluorescent antibodies for the zeta (zeta), epsilon (epsilon) and gamma (gamma) globin chains. The percentage of fetal cells positive for each stain was calculated. Fluorescence in-situ hybridization (FISH) for X and Y chromosomes was also performed. RESULTS: The percentage of erythroblasts enriched from maternal blood that stained positive for zeta, epsilon and gamma globin chains and with Kleihauer-Giemsa was significantly higher in the multifetal compared with singleton pregnancies. The median enriched percentage of positively stained erythroblasts was about three times higher in the twin than in singleton pregnancies (P < 0.0001), nearly twice as high in the triplet than in twin pregnancies (P < 0.01) and five times higher in the triplet than singleton pregnancies (P < 0.0001). FISH for Y chromosome confirmed the increase in fetal cell proportion in the multifetal pregnancies. CONCLUSIONS: These findings suggest that there is an increase in the physiological feto-maternal cell trafficking in multifetal pregnancies compared with singleton pregnancies, which is likely to be due to the increased placental surface area and vasculature.

Adult↗
PubMed2000

Prenatal diagnosis of beta-thalassaemia using fetal erythroblasts enriched from maternal blood by a novel gradient.

We have assessed a new technique for the isolation of fetal erythroblasts from maternal blood for the non-invasive prenatal diagnosis of pregnancies at risk of beta-thalassaemia. This method relies on the separation of erythroblasts from maternal nucleated cells by a novel step gradient and high speed centrifugation. In four of the six cases examined, single erythroblasts were identified by immunohistochemistry for zeta (zeta) globin. These were individually micromanipulated and analysed by single cell polymerase chain reaction (PCR) and subsequent sequencing of the region of beta-globin locus where the mutations most common to the region of Puglia, Italy, are clustered. In each of the four instances where fetal erythroblasts were identified by antibody staining, the fetal beta-globin genotype was correctly determined. To date, this represents the largest series of non-invasive prenatal diagnoses performed for this haemoglobinopathy.

Centrifugation, Density Gradient↗
PubMed1996

Erythroblastic and/or megakaryoblastic leukemia in Down syndrome: treatment with low-dose arabinosyl cytosine.

PURPOSE: We report here the clinical response to low-dose arabinosyl cytosine (Ara-C) in seven children with Down syndrome (DS) and acute leukemia in which blast cells express markers of erythroid and/or megakaryoblastic lineages. Following an initial course of treatment with Ara-C, complete remission was obtained in all seven patients. Maintenance therapy with Ara-C was continued during complete remission. Four patients subsequently relapsed; the three others are disease-free. Based on these data, we suggest that when conventional therapy is contraindicated by associated malformations, low-dose Ara-C can be used for treating DS patients with erythroblastic or megakaryoblastic leukemia. The aim of this study was to assess the efficacy of low-dose Ara-C in treating megakaryoblastic and/or erythroblastic leukemia associated with DS. PATIENTS AND METHODS: Seven patients with DS presented with leukemia in which blast cells displayed early markers of the erythroblastic and/or megakaryoblastic lineage. Low-dose subcutaneous Ara-C (10 mg/m2 two times per day) was given for 21 days as induction therapy, followed by a 5-10-day course each month for 2 years as a maintenance treatment. RESULTS: Low-dose Ara-C treatment resulted in complete remission in all seven patients and in long-term disease-free survival in three patients. CONCLUSION: In cases in which conventional chemotherapy is contraindicated, low-dose Ara-C should be considered as a therapeutic alternative for treatment of DS-associated erythroblastic or megakaryocytic leukemia.

Antimetabolites, Antineoplastic↗
PubMed1980

Congenital dyserythropoietic anaemia type I: absence of clonal expression in the nuclear abnormalities of cultured erythroblasts.

Erythroid colonies derived from the circulating early erythroid precursor (BFU-E) of a patient with congenital dyserythropoietic anaemia type I (CDA I) have been grown in plasma clot and studied by electron microscopy. The number of circulating BFU-E was in the normal range with a roughly normal appearance at the light microscopic level. However, investigation of individual colonies by electron microscopy has always shown a mixture of normal and abnormal erythroblasts exhibiting the typical nuclear aberrations found in vivo. The proportion of normal erythroblasts varied from one colony to another. After the release of the cells from the clot in order to permit new cellular interactions, macrophages were observed to phagocytose abnormal erythroblasts but also a few erythroblasts with normal nuclei. These findings demonstrate that CDA I is a disorder which results from a defective erythroid stem cell but that the progeny of each BFU-E may vary considerably in the extent to which they express the morphological defects. Based on studies of cultures of BFU-E, similar conclusions were previously made for CDA II.

Adult↗