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PubMed2005

[The effect of Siwu Tang on EPO and G-CSF gene expression in bone marrow of irradiated blood deficiency mice].

OBJECTIVE: To observe the blood enriching function of Siwu Tang and its effect on Epo and G-CSF gene expressions in bone marrow of blood deficiency mice, and thus provide the basis for understanding the molecular mechanism of blood enriching function of Siwu Tang. METHOD: The animal model of blood deficiency were established in the mice by using 3.5 Gy60Co gamma-ray. Peripheral blood cells were analyzed and CFU-GM, BFU-E, CFU-E and CFU-mix were counted in bone marrow colony cultured. Both Epo and G-CSF gene expressions in bone marrow were measured with RT-PCR. RESULT: Siwu Tang significantly increased the number of peripheral blood cells and the amount of CFU-GM, BFU-E, CFU-E and CFU-mix in bone marrow and enhanced Epo and G-CSF gene expression in bone marrow in the mice with blood deficiency. CONCLUSION: The promotion of Epo and G-CSF gene expressions in bone marrow may be one of the mechanisms underlying the blood enriching function of Siwu Tang decoction.

Animals↗

PubMed1990

Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation.

Because human P40 T-cell growth factor, tentatively designated interleukin-9 (IL-9), was isolated through its ability to stimulate a human IL-3-dependent leukemic cell line (M-O7E), we tested the ability of IL-9 to support the growth and differentiation of normal hematopoietic progenitor cells from peripheral blood and bone marrow. Although the M-O7E cell line was derived from a patient with megakaryoblastic leukemia, IL-9 has not proved to be a growth or maturation factor for megakaryocytes, but instead has proved to be effective in supporting the development of erythroid bursts (BFU-E) in cultures supplemented with erythropoietin. Using highly purified progenitors from peripheral blood, IL-3 showed a BFU-E plating efficiency of 46% compared with 20% for IL-9. Because of the purity of these cell preparations and the low cell density in culture, IL-9 is likely to interact directly with erythroid progenitors. Analysis of mixing experiments and of the morphology of the BFU-E in culture indicated that IL-9 interacts preferentially with a relatively early population of IL-3-responsive BFU-E. In cultures of human bone marrow or cord blood, IL-9 selectively supported erythroid colony formation, while IL-3 and granulocyte/macrophage colony-stimulating factor additionally yielded granulocyte/macrophage colonies. Therefore, IL-9 represents a new T cell-derived cytokine with the potential for selectively stimulating erythroid development in the hematopoietic system.

Antigens, CD↗

PubMed1991

Detection of micrometastases from primary breast cancer.

The monoclonal antibody LICR-LON-M8 was used in a series of experiments to determine how an immunohistochemical technique could be used as a diagnostic test for micrometastatic disease in patients with operable, primary breast carcinoma. Optimal tissue and antigen preservation was obtained with fixatives containing either picric acid or a heavy metal such as mercury to allow staining with the monoclonal antibody diluted to 1:12,000 to 1:16,000 from unpurified mouse ascites. Tissue affected by primary and metastatic disease stains in a characteristic fashion, which is distinct from benign breast tissue. All the ductal tumours stained positively for malignant cells with the monoclonal antibody preparation. Within the bone marrow, occasional granulocytes and granulocyte precursors stained positively if the endogenous peroxidase activity was incompletely blocked. These cells were readily differentiated from tumour cells on cytologic examination. With these monoclonal antibody and immunohistochemical staining techniques it may now be possible to detect early micrometastatic disease in the bone marrow of patients with primary breast cancer.

Antibodies, Monoclonal↗

PubMed1991

A coenzyme A-independent transacylase is linked to the formation of platelet-activating factor (PAF) by generating the lyso-PAF intermediate in the remodeling pathway.

The remodeling pathway for the biosynthesis of platelet-activating factor (PAF) consists of the following reaction sequence: alkylacylglycerophosphocholine----lyso-PAF----PAF. Results presented in this article describe a novel transacylase activity that generates the lyso-PAF intermediate, which can then be acetylated to form PAF. Ethanolamine-containing lysoplasmalogens, 1-acyl-2-lyso-sn-glycero-3-phosphoethanolamine, alkyllysophosphoethanolamine, unlabeled lyso-PAF, 1-acyl-2-lyso-GPC, where GPC is sn-glycero-3-phosphocholine, and choline-containing lysoplasmalogens were all able to stimulate the formation of [3H]lyso-PAF from a [3H]alkylacyl-GPC precursor pool associated with HL-60 cell (granulocytic type) membranes. Other glycerolipids containing free hydroxyl groups (3-alkyl-2-lyso-sn-glycero-1-phosphocholine, lysophosphatidylserine, lysophosphatidylinositol, diacylglycerols, alkylglycerols, and monoacylglycerols), cholesterol, phosphatidylcholine, and phosphatidylethanolamine had no stimulatory effect on the release of [3H]lyso-PAF from the prelabeled membranes under identical incubation conditions. The observed transacylase reaction is directly coupled to PAF production, since the addition of a lysoethanolamine plasmalogen preparation to HL-60 membranes in the presence of [14C]acetyl-CoA stimulated PAF formation; under these conditions the lysoethanolamine plasmalogen was acylated. The transacylase responsible for the release of lyso-PAF from the membrane-associated alkylacyl-GPC was not affected by Ca2+, EGTA, or a known phospholipase A2 inhibitor, p-bromophenacyl bromide. The fact that the unnatural analog of lyso-PAF, lysophosphatidylserine, and lysophosphatidylinositol did not influence transacylase activity, whereas detergents such as deoxycholate and Triton X-100 inhibited the activity, demonstrated the observed stimulatory effects of the choline- and ethanolamine-containing lysophospholipids on the formation of [3H]lyso-PAF from [3H]alkylacyl-GPC were not due to any detergent property of these lysophospholipids. Thus, we conclude a CoA-independent transacylase (possessing phospholipase A2/acyltransferase activities) can be responsible for the formation of the lyso-PAF intermediate in the remodeling route of PAF biosynthesis.

Acyltransferases↗

PubMed1990

In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes.

Erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring the in vitro response of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors from 12 patients and from eight healthy donors to recombinant human erythropoietin (rhEPO), and by quantifying relationships between circulating EPO levels and progenitor cell frequencies in MDS marrow. Half-maximal growth of MDS CFU-E and BFU-E was detected at a 4-fold higher rhEPO concentration than required by control erythroid progenitors. Nine of the patients evaluated exhibited maximal growth of erythroid colonies at 5- to 20-fold higher than control saturating rhEPO concentrations. Circulating EPO levels in MDS patients were elevated, with a mean value approximately 35-fold higher than that of controls. The frequency of MDS marrow CFU-E and BFU-E was 57 +/- 42% and 18 +/- 9% of the mean control values, respectively. Correlation analysis of the relationships between MDS EPO levels and erythroid progenitors indicated that the anemia in MDS is not attributable to an abnormality in the capacity of EPO to induce the generation of CFU-E, but may be influenced by the BFU-E population, whose severe deficiency results in insufficient influx of EPO-responsive cells. Our findings therefore suggest that treatment of MDS patients with rhEPO may be of limited benefit, since the generation of BFU-E from more primitive ancestors and the initial growth requirements of these cells are not under the regulatory influence of this hormone.

Adolescent↗

PubMed1989

[Hemopoietic precursor cells in the intima of the atheromatous human aorta].

Granulocyte-macrophage progenitor cells (CFU-GM) were found in the intima of human atheromatous aorta. Granulocyte-macrophage colonies were recovered on the 14th day of culturing of intimal cells suspensions on agar. Medium conditioned by normal leukocytes in the presence of phytohaemagglutinin was used as a source of the colony-stimulating factor. Grossly normal and atheromatous intima contained different number of CFU-GM. No GM were recovered from fibrous plaques. By light and electron microscopies, the injured aortic intima contained the clusters of blood-born cells that were at various stages of granulocytopoiesis (including blasts and mature cells) and poorly differentiated lymphocyte-like cells. The results obtained suggest that in human aortic intima proliferation and differentiation of CFU-GM occur at early stages of atherogenesis, prior to fibrous plaque formation.

Adult↗

PubMed1993

Different responses of human marrow and circulating erythroid progenitors to stem cell factor, interleukin-3 and granulocyte/macrophage colony-stimulating factor.

The effects of recombinant human stem cell factor (SCF/c-kit ligand), interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) on erythroid colony formation by non-phagocytic mononuclear cells (MNC) and CD34+ cells derived from normal human bone marrow (BM), peripheral blood (PB) and umbilical cord blood (CB) were studied using a methylcellulose culture containing recombinant human erythropoietin (Epo). BM-MNC generated the largest number of total erythroid colonies consisting of erythroid bursts and erythroid mixed colonies (E-Mix) in the presence of SCF, whereas PB-MNC produced the largest number with IL-3. No additive effect between SCF and IL-3 was observed in the erythroid colony formation by BM- or PB-MNC. These observations were reproducible in cultures with several independent samples and purified CD34+ cells, suggesting that in normal human adults the erythroid progenitors supported by SCF alone mainly reside in the BM but those supported by IL-3 alone are mainly circulating. IL-3 was the most potent promoter of the total erythroid colony formation by CB-MNC, but it had no cooperation with SCF. In contrast, SCF supported large numbers of E-Mix and showed significant cooperative activity with IL-3 in E-Mix formation. These findings were also confirmed using independent specimens and CD34+ cells. Outstanding E-Mix formation by the CB cells indicated that newborn infants contain significantly more immature circulating erythroid progenitors than adults. These observations will stimulate interest in the role of the c-kit-SCF system as an adhesion molecule in the ontogenetic development of hemopoiesis.

Adult↗

PubMed1994

Mast cell growth factor (c-kit ligand) restores growth of multipotent progenitors in myelodysplastic syndrome.

In vitro growth of primitive hematopoietic progenitors is severely impaired in the myelodysplastic syndromes (MDS). To determine if the c-kit ligand mast cell growth factor (MGF) can improve progenitor growth in MDS, we evaluated in vitro responsiveness of bone marrow progenitors from 25 patients to MGF and/or GM-CSF, interleukin-3 (IL-3) and PIXY 321, and examined the relationship between progenitor response and cellular expression of the c-kit receptor. MGF and erythropoietin gave rise to macroscopic colonies and dose-dependently increased CFU-GEMM and BFU-E up to 27-fold in 15 (60%) and 20 (80%) patients, respectively. Among 17 patients with absent growth in lymphocyte-conditioned media, MGF stimulated CFU-GEMM recovery in 59%, compared to 23% with PIXY 321, 12% with IL-3 and 8% with GM-CSF. Cytokine combinations did not augment recovery of erythropoietin-dependent progenitors above that achieved with MGF alone. MGF and/or IL-3 were comparatively weak stimulants of CFU-GM formation, whereas GM-CSF and PIXY in combination with MGF increased colony number 2- to 15-fold in 60 and 70% of patients, respectively, while preserving maturation competence as evidenced by colony composition and increased colony/cluster ratio. The stimulatory effects of MGF were observed in all morphologic categories of MDS except chronic myelomonocytic leukemia. A mononuclear cell population expressing the c-kit receptor was identified by flow cytometry in 57% of cases. Neither SR-1 reactivity nor cytogenetic pattern predicted progenitor response to MGF. These data indicate that MGF improves the colony-forming capacity of hematopoietic progenitors in MDS and is a potent co-stimulant of multipotent and committed progenitor recovery. The heterogeneity in MGF responsiveness implies an intrinsic defect in growth regulation not explained by cellular loss of c-kit display.

Adolescent↗

PubMed1995

[Intensive chemotherapy with support of peripheral hematopoietic progenitor cells, mobilized with high-dose cyclophosphamide and G-CSF: fast hematologic recovery].

BACKGROUND: Hematopoietic progenitor cells mobilized to peripheral blood by a chemotherapy combined or not with hematopoietic growth factors and harvested with cyto-apheresis (CTA) provide a rapid hematological recovery when infused as a support step after intensive chemotherapy (IC). METHODS: Cyclophosphamide (CI) 4 g/m2 and G-CSF 5 mcg/kg/d were administered to 19 patients with a solid tumor or lymphoma. Daily CTA were performed during hematological recovery to harvest > 2.5 x 10(6) cells CD34+/kg. Seventeen patients received IC with infusion of peripheral hematopoietic progenitor cells (PHPC) and G-CSF. RESULTS: A total of 52 CTA were performed, with a median (M) of 2 per patient. A M of 4.4 x 10(8) mononucleated cells/kg and 9.8 x 10(6) CD34+/kg were harvested per patient. Hematological recovery after IC with support of PHPC and G-CSF was rapid in all cases, but the aplastic period was shorter in the ten patients who received > 5 x 10(6) CD34+/kg cells than in the seven patients with < 5 x 10(6) kg: The median of recovery to neutrophils > 0.5 x 10(9)/l was 8 days compared with 9 days (p = 0.0005), to platelets > 20 x 10(9)/l of 8 days compared with 12 days (p = 0.001), and to platelets > 50 x 10(9)/l of 11 days compared with 14 days (p = 0.001). CONCLUSIONS: Toxicity of IC (4 g/m2) with G-CSF is moderate and allows the harvesting of an adequate number of PHPC. Its infusion after IC provides a rapid hematological recovery, which was more marked in patients receiving 5 x 10(6) CD34+/kg cells, than with the same IC schedules of IC with autologous bone marrow transplantation.

Adult↗

PubMed1994

Identification and dynamics of paraquat in the bone marrow, thymus and spleen in rats using immunohistochemical techniques.

We reported the immunohistochemical identification of paraquat in the immune and hematopoietic systems such as bone marrow, spleen and thymus. Twelve paraquat-poisoned rats were sacrificed in 3 h, 12 h, 3 days, 7 days and 10 days after intravenous administration of paraquat. In the bone marrow, paraquat was localized in several types of blood cells (granulocyte, erythrocyte and megakaryocyte) and their precursors between 24 h and 7 days after the injection. In the thymus, paraquat was mainly localized in the medulla between 12 h and 7 days after the injection, whereas in the spleen, it was mainly localized in the red pulp between 12 h and 10 days after administration of paraquat.

Animals↗

PubMed1993

Toward cord blood banking: density-separation and cryopreservation of cord blood progenitors.

It has been shown that cord blood collected at birth can be used to successfully engraft a human lymphocyte antigen (HLA)-matched sibling suffering from a malignant disease. It has been further suggested that this source of cells may be used in unrelated but HLA-compatible patients. These wide indications would imply the establishment of cord blood banks comprising 10(5) or more samples. In this report we show that it is possible to fractionate and freeze cord blood samples without major loss in granulomonocytic or erythroblastic progenitors (CFU-GM and BFU-E). Density separation should be carried out using Percoll of density 1.080. Separated samples should be frozen and thawed in the presence of DNase I. This procedure should allow the storage of approximately 10 mL samples in cryotubes containing a number of CFU-GM and BFU-E sufficient to engraft a patient weighing less than 30 kg. These data provide a rationale for establishing cord blood banks.

Blood Banks↗

PubMed1995

Inhibition of hematopoiesis by a plasma factor in a case of aplastic anemia associated with systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) may be associated with inhibition of hematopoiesis mediated by antibodies, T-cells or both. A 41-year-old woman with a five-year history of SLE treated with prednisone was admitted to Cabrini Medical Center in New York. The patient complained of fever, chills, arthralgias, general malaise, weakness and dyspnea on exertion, and showed malar rash, pallor, and a systolic ejection murmur along the left sternal border. Admission work up included a CBC with evidence of moderate pancytopenia, a normal EKG, and a normal chest X-ray. The patient's anemia was symptomatic and required a transfusion of packed red blood cells (PRBC's). Bone marrow biopsy and aspiration revealed an aplastic marrow with few hypoplastic islands of hematopoietic elements. The patient was treated with plasmapheresis, achieving immediate progress towards recovery. Bone marrow culture studies (erythroid BFU-E, and myeloid CFU-GM) were done by incubating various titers of the patient's acute phase plasma with normal bone marrow cells. This was done to determine if the patient's plasma contained any hematopoietic inhibitory activity, as has been reported in other cases. Our experiments demonstrated marked inhibition of erymathropoiesis and myelopoiesis in vitro, when various titers of the patient's plasma were included in the culture media. Control plasma produced no inhibition. These studies support the hypothesis that a circulating antibody which inhibits hematopoiesis may be produced in SLE patients with aplastic anemia, and be responsible for it.

Adult↗

PubMed1993

The influence of synthetic peptide from retroviral transmembrane protein p15E on murine spleen cell proliferation and bone marrow hemopoietic precursor colony formation.

The retroviral transmembrane p15E peptide is known to suppress a wide variety of immune cell functions, suggesting a role for immunosuppression associated with retroviral infection. The 10-amino acid sequence from the highly conserved portion of p15E (CKS-10) is capable of reproducing this inhibitory activity. In this study we set out to determine the influence of this decapeptide on murine spleen cell mitogen-induced proliferation and hematopoietic granulocyte-macrophage and erythroid precursor colony formation in vitro. A dose- and time-dependent suppression of spleen cell blastogenic response was produced by the CKS-10 peptide. When bone marrow cells were incubated with decapeptide, the significant decrease of CFU-GM colony number was also dose-dependent. In contrast, the same doses of CKS-10 peptide which induced a most significant inhibition of CFU-GM colony formation caused a marked increase of BFU-E colonies. A most pronounced effect of the peptide on bone marrow hematopoietic progenitor activity was produced by prolonged exposure to the peptide. Given the results of this study, it seems likely that, in addition to the cytopathic effect of retroviruses on the lymphocytes, viral peptide-mediated hematopoiesis disorders may also play an important role in the pathogenesis of immunodeficiency associated with retroviral infections.

Animals↗

PubMed2006

Involvement of suppressors of cytokine signaling in toll-like receptor-mediated block of dendritic cell differentiation.

Dendritic cells (DCs) are important sentinels within innate immunity, monitoring the presence of infectious microorganisms. They operate in 2 different maturation stages, with transition from immature to mature DCs being induced by activation of toll-like receptors (TLRs). However, TLRs are also expressed on precursor cells of DCs. Here we analyzed the effects of TLR stimulation during the process of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-mediated in vitro generation of immature DCs from precursor cells. We show that TLR triggering deviated phenotypic and functional differentiation from CD14+ monocytes to CD1a+ DCs. Similar results were obtained when differentiation of murine myeloid DCs from bone marrow cells was analyzed. The inhibitory effects were independent of soluble factors. TLR stimulation in DC precursor cells induced proteins of the suppressor of cytokine signaling family (SOCS), which correlated with loss of sensitivity to GM-CSF. Overexpression of SOCS-1 abolished GM-CSF signal transduction. Moreover, forced SOCS-1 expression in DC precursors mimicked the inhibitory effects on DC generation observed for TLR stimulation. The results indicate that TLR stimulation during the period of DC generation interferes with and deviates DC differentiation and that these effects are mediated particularly by SOCS-1.

Animals↗

PubMed1998

G-CSF receptor-mediated up-regulation of c-fos but not c-raf mRNA expression in myeloid cells.

Granulocyte colony stimulating factor (G-CSF) regulates survival, proliferation, and differentiation of myeloid precursor cells. One of the signaling mechanisms for the G-CSF receptor (G-CSF-R) involves the activation of Ras/MAP kinase (MEK) pathway. Since Raf is an important, common link between Ras and MEK in the Ras-Raf-MEK cascade, we studied the expression of c-raf mRNA in G-CSF-treated myeloid precursor cell lines--NFS-60 and HL-60. G-CSF did not alter c-raf mRNA expression in these cells up to 24 h, but induced a transient up-regulation of c-fos mRNA expression between 15-60 min post-treatment. Our results show that G-CSF triggers a de novo induction of c-fos but not c-raf mRNA, and suggests that G-CSF-R-mediated activation of Ras/MEK pathway may involve post-transcriptional mechanisms of Raf regulation.

Bone Marrow Cells↗

PubMed2006

G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells.

CXCR4 receptor expression is required for the retention of granulocyte precursors and mature neutrophils within the bone marrow, and disruption of the SDF-1/CXCR4 axis in the bone marrow results in the mobilization of myeloid lineage cells to the peripheral circulation. We report that G-CSF down-regulates CXCR4 expression in bone marrow-derived murine and human myeloid lineage cells. When exposed to G-CSF, murine Gr1(+) bone marrow myeloid cells display a time-dependent reduction of cell-surface CXCR4 and respond poorly to SDF-1 in attachment and migration assays. Bone marrow-derived cells of nonmyeloid lineage display no change in surface CXCR4 expression upon exposure to G-CSF. Compared with controls, mice treated with G-CSF for mobilization of hematopoietic progenitor cells display reduced levels of CXCR4 selectively in bone marrow Gr1(+) myeloid cells. Since bone marrow myeloid cells express G-CSF receptors and G-CSF rapidly reduces CXCR4 expression in purified Gr1(+) cells populations, these results provide evidence that G-CSF acts directly on myeloid lineage cells to reduce CXCR4 expression. By down-regulating CXCR4 expression in bone marrow myeloid cells and attenuating their responsiveness to SDF-1, G-CSF promotes their mobilization from the bone marrow to the peripheral blood.

Animals↗

PubMed2006

A karyometric note on nucleoli in human early granulocytic precursors.

The diameter of nucleoli was measured in human bone marrow early granulocytic precursors after visualization by a simple cytochemical method for demonstration of RNA. Such method facilitated to clearly see nucleolar bodies without perinucleolar chromatin, including those of micronucleoli. The bone marrow of patients suffering from chronic myeloid leukaemia (untreated with cytostatics) provided a satisfactory number of both myeloblasts and promyelocytes for nucleolar measurements because of prevailing granulopoiesis. The direct nucleolar measurement was carried out on digitized and processed images on the screen at magnification 4,300x. It seems to be likely that the nucleolar size is directly related to the number of nucleoli per cell. The largest nucleoli were present in both myeloblasts and promyelocytes that possessed a single nucleolus. In contrast, the nucleolar diameter was significantly smaller in cells with multiple nucleoli. However, in cells with small multiple nucleoli, one of them was always larger and dominant with a large number of AgNORs. Such large nucleoli are possibly visible in specimens stained with panoptic procedures or methods staining nuclear chromatin or DNA. It should also be mentioned that both myeloblasts and promyelocytes mostly possessed two nucleoli with the mean diameter close to 1.5 microm. The incidence of early granulocytic precursors classified according to the nucleolar number and size strongly suggested that the various nucleolar number and nucleolar size in these cells might be related to the different stage of the cell cycle and might also explain their heterogeneity.

Cell Nucleolus↗

PubMed1997

[New developments in understanding the compensatory hematological reactions and their outcomes in local fractionated therapeutic gamma irradiation].

We have carried out a study of the bone marrow status in both irradiated and non-irradiated zones of 56 patients with stage I-II Hodgkin's disease in complete 9-12 (33 patients, group 1) and 18-23 (23 patients, group 2) year remission after therapeutic irradiation of the supradiaphragmatic lymphatic collectors at a dose of 40 Gy with irradiation of the spleen (33 patients) or splenectomy (23 patients). The total count of myelokaryocytes, myelogram, a relative and absolute content of lymphoid cells, immature granulocytes and elements of erythroid series were calculated in the aspirates from the exposed to radiotherapy sternum and non-irradiated upper portion of the ileum. The number of granulocyte-macrophage (CFU-GM) and stromal (CFU-F) precursor cells were defined using in vitro culture technique. There was a complete annihilation of the bone marrow in the irradiated zones, when the dose exceeded 35 Gy in 3-4 weeks. The concentration of myelokaryocytes, immature granulocytes, erythronormoblasts, CFU-GM, CFU-F in non-exposed bone marrow were significantly lower in all patients of group 2 than in normal subjects and in group 1 patients. Absolute lymphoid count in patients with 18-23 year remission was found to be normal but was considerably reduced in comparison to patients of group 1. These changes may be the result of the previous hyperactivity of the non-irradiated bone marrow which could be a cause of stem cell compartment depletion. The differential calculation of compact and diffuse subpopulations of CFU-F revealed a significant reduction of compact colony-forming CFU-F in both irradiated and unexposed bone marrow. Almost all the stromal precursor cells from irradiated zone formed diffuse colonies in cultures. These results confirm experimental data concerning greater radiosensitivity and proliferative potential of CFU-F, forming compact colonies versus diffuse colony-forming CFU-F. Aplasia of the irradiated bone marrow and hypoplasia of the non-irradiated bone marrow 18-23 years after radiotherapy completion coexisted with normal circulating CFU-GM and granulocyte blood count suggesting a compensatory mechanism involving a mitotic amplification between the progenitor cell and the final differentiated cell.

Adult↗