Biomedical subjects

C A Bennett

Publications and source records attributed to C A Bennett.

At least 19 recordsLinked to original sources

PubMed2000

Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.

The t(12;21)(p13;q22) chromosomal translocation is the most frequent illegitimate gene recombination in a pediatric cancer and occurs in approximately 25% of common acute lymphoblastic leukemia (cALL) cases. This rearrangement results in the in frame fusion of the 5'-region of the ETS-related gene, TEL (ETV6), to almost the entire acute myeloid leukemia 1 (AML1) (also called CBFA2 or PEBP2AB1) locus and expression of the TEL-AML1 chimeric protein. Although AML1 stimulates transcription, TEL-AML1 functions as a repressor of some AML1 target genes. In contrast to the wild type AML1 protein, both TEL and TEL-AML1 interact with N-CoR, a component of the nuclear receptor corepressor complex with histone deacetylase activity. The interaction between TEL and N-CoR requires the central region of TEL, which is retained in TEL-AML1, and TEL lacking this domain is impaired in transcriptional repression. Taken together, our results suggest that TEL-AML1 may contribute to leukemogenesis by recruiting N-CoR to AML1 target genes and thus imposing an altered pattern of their expression.

Core Binding Factor Alpha 2 Subunit↗

PubMed2000

TEL-AML1 fusion gene frequency in paediatric acute lymphoblastic leukaemia in Brazil.

We analysed 67 samples from Brazilian children of diverse ethnic origins with acute lymphoblastic leukaemia (ALL) for the presence of the TEL-AML1 fusion gene transcripts using reverse transcription polymerase chain reaction (RT-PCR). All 12 positive cases (20% of the 60 B-cell precursor ALL) had common (CD10+) ALL with a mean age of 4 years (range 1-10 years). We conclude that the frequency, age, distribution and clinical features of the TEL-AML1 fusion gene-positive ALL is similar in the diverse ethnic backgrounds of the Brazilian children to that in other countries with predominantly white Caucasian or oriental ethnicity. Apparent exceptions to this generality are discussed.

Black People↗

PubMed1999

Application of the fundamental parameter method to the in vivo x-ray fluorescence analysis of Pt.

The application of the fundamental parameter method (FPM) to the in vivo x-ray fluorescence (XRF) analysis of Pt has been investigated. The FPM is conventionally used to carry out elemental analysis of samples in vitro without the need to use standard samples of accurately known composition for system calibration. The present work has involved the use of the FPM to calculate the concentration of Pt solutions in phantoms, with concentrations ranging from 25-1000 ppm. The phantoms simulate the measurement of Pt-based chemotherapy drugs in head and neck tumours. The radiation sources were a 150 kV tungsten-anode x-ray tube and the isotope 99mTc. The minimum detection limit measured for Pt was in the range 8-30 ppm (depending on radiation source and geometry), using a narrow (5 mm) diameter beam. Dose rates in the phantom were 0.1-5 mGy h(-1). Average differences between nominal and calculated values of Pt concentration were <8% using the phantoms in air to simulate measurement of Pt in superficial body sites. If the phantoms were placed in a water bath, to simulate measurement at greater depths of overlying tissue, higher systematic differences (15-20%) were observed. This effect is probably due to multiple scattering processes in the surrounding medium.

Biophysical Phenomena↗

PubMed1999

The optimum time to initiate habitual xylitol gum-chewing for obtaining long-term caries prevention.

Habitual xylitol gum-chewing may have a long-term preventive effect by reducing the caries risk for several years after the habitual chewing has ended. The goal of this report was (1) to determine if sorbitol and sorbitol/xylitol mixtures provide a long-term benefit, and (2) to determine which teeth benefit most from two-year habitual gum-chewing - those erupting before, during, or after habitual gum-chewing. Children, on average 6 years old, chewed gums sweetened with xylitol, sorbitol, or xylitol/sorbitol mixtures. There was a "no-gum" control group. Five years after the two-year program of habitual gum-chewing ended, 288 children were re-examined. Compared with the no-gum group, sorbitol gums had no significant long-term effect (relative risk [RR], 0.65; 95% confidence interval [c.i.], 0.39 to 1.07; p < 0.18). Xylitol gum and, to a lesser extent, xylitol/sorbitol gum had a long-term preventive effect. During the 5 years after habitual gum-chewing ended, xylitol gums reduced the caries risk 59% (RR, 0.41; 95% c.i., 0.23 to 0.75; p < 0.0034). Xylitol-sorbitol gums reduced the caries risk 44% (RR, 0.56; 95% c.i., 0.36 to 0.89; p < 0.02). The long-term caries risk reduction associated with xylitol strongly depended on when teeth erupted (p < 0.02). Teeth that erupted after 1 year of gum-chewing or after the two-year habitual gum use ended had long-term caries risk reductions of 93% (p < 0.0054) and 88% (p < 0.0004), respectively. Teeth that erupted before the gum-chewing started had no significant long-term prevention (p < 0.30). We concluded that for long-term caries-preventive effects to be maximized, habitual xylitol gum-chewing should be started at least one year before permanent teeth erupt.

Belize↗

PubMed1998

Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.

The TEL (ETV6)-AML1 (CBFA2) gene fusion is the most common reciprocal chromosomal rearrangement in childhood cancer occurring in approximately 25% of the most predominant subtype of leukemia- common acute lymphoblastic leukemia. The TEL-AML1 genomic sequence has been characterized in a pair of monozygotic twins diagnosed at ages 3 years, 6 months and 4 years, 10 months with common acute lymphoblastic leukemia. The twin leukemic DNA shared the same unique (or clonotypic) but nonconstitutive TEL-AML1 fusion sequence. The most plausible explanation for this finding is a single cell origin of the TEL-AML fusion in one fetus in utero, probably as a leukemia-initiating mutation, followed by intraplacental metastasis of clonal progeny to the other twin. Clonal identity is further supported by the finding that the leukemic cells in the two twins shared an identical rearranged IGH allele. These data have implications for the etiology and natural history of childhood leukemia.

Amino Acid Sequence↗

PubMed1998

Characterization of the heparin-binding properties of human clusterin.

Clusterin is a highly conserved mammalian glycoprotein which has been predicted to contain heparin-binding sites. We tested this prediction by studying the interactions between heparin and clusterin using ELISA and heparin affinity chromatography methodologies. Two forms of biotinylated heparin were used in ELISA: heparin which had been directly biotinylated with a biotin-N-hydroxysuccinimide ester and heparin which had been activated using epichlorohydrin and 1,6-diaminohexane prior to biotinylation. Both gave dose-dependent increases in ELISA signal with increasing concentrations of biotinylated heparin, with the latter giving signals an order of magnitude greater than the former. There was a dose-dependent increase in the ELISA signal from bound biotinylated heparin with increasing concentrations of plate-bound clusterin. The apparent affinity constant for binding of biotinylated heparin to plate-bound clusterin at pH 6.0 was estimated as 0.06 +/- 0.02 microM. Unlabeled heparin blocked the binding of biotinylated heparin to clusterin over a concentration range similar to that of the binding of biotinylated heparin to plate-bound clusterin. The binding of biotinylated heparin to clusterin was independent of the presence or absence of Ca2+. The binding of biotinylated heparin to plate-bound clusterin increased with decreasing pH over the range 5.5-8.0 and was characterized by an apparent pKa of 6.9. Clusterin in human serum bound to heparin-Sepharose at pH 6.0 but not at pH 7.4. Dot-blot experiments showed that one of the polypeptide chains of clusterin which had been reduced and alkylated under denaturing conditions bound to heparin-Sepharose. This chain was identified as the alpha chain from its N-terminal amino acid sequence.

Biotin↗

PubMed1998

Plane polarized x-ray fluorescence system for the in vivo measurement of platinum in head and neck tumours.

A plane polarized x-ray fluorescence system based on an orthovoltage radiotherapy treatment unit, the Pantak DXT-300, has been developed and optimized to measure tumour platinum concentration. The platinum derives from platinum based chemotherapy agents, such as cisplatin and carboplatin used to treat tumours in the head and neck region. Photons from an x-ray tube are polarized by scattering through 90 degrees, and used to stimulate the emission of characteristic platinum x-rays from the tumour. Information about the drug in the tumour could be of use in establishing dose-response relationships, in order to optimize the treatment and reduce the toxicity of the drug. The performance of the system was optimized with respect to the applied x-ray tube voltage, the current and the filter material; the effect on the minimum detection limit (MDL) of the thickness of the overlying tissue surrounding the tumour was investigated in detail. The lowest MDL is achieved using 0.25 mm of tin filter and x-ray tube voltage of 220 kV. This is 5.6 ppm for a tumour surrounded with 20 mm of overlying tissue, a measurement time of 2000 s and an estimated skin dose of 3.0 mGy. This represents the most sensitive in vivo XRF system to date. We have embarked on a clinical pilot study to measure the platinum concentration in tumours of the head and neck, and expect initial results to be available in the near future.

Cisplatin↗

PubMed1998

A descriptive report of the effects of a 16-month xylitol chewing-gum programme subsequent to a 40-month sucrose gum programme.

A previous caries trial (Belize studies) involved the usage of sucrose chewing-gum for a period of 40 months in one group of initially 10-year-old subjects in an environment of high sugar consumption, high caries activity, and limited access to restorative care. After the termination of the 40-month supervised sucrose gum usage, the 109 subjects of the original sucrose group retrieved at the endpoint of the original trial were invited to participate in a xylitol chewing-gum programme (involving the usage of the '100% pellet-shaped formular') for 16 months. The average daily consumption level of xylitol was up to 14 g per subject, normally used in seven daily chewing episodes. Although most subjects used chewing-gum at schools and received their gum portions from a school official, gum chewing during these 16 months was mostly unsupervised. After 16 months, 83 subjects (76%; mean age 14.9 years) were retrieved. The caries status of these subjects was examined by the same calibrated, blinded examiners as in the original trial. To mask the examiners, 141 similar non-participating subjects were recruited from the same school classes and were examined in a random order with the gum-using subjects, according to the same standard routine. The intensified xylitol gum usage for 16 months was associated with a reduction of the mean DMFS score from 10.9 (at 40 months) to 9.3 (at 56 months, p = 0.0013) and a reduction in caries rate from 20.1 caries onsets per 1,000 surface-years (40-month period average rate) to 10.2 caries onsets per 1,000 surface-years. The reduction in DMFS score resulted mostly from the change in the D component of the index and possibly reflected a stabilisation of the caries process and rehardening of some caries lesions to a non-progressive carious state.

Adolescent↗

PubMed1996

Regulation of the myeloperoxidase enhancer binding proteins Pu1, C-EBP alpha, -beta, and -delta during granulocyte-lineage specification.

We have compared the molecular architecture and function of the myeloperoxidase upstream enhancer in multipotential versus granulocyte-committed hematopoietic progenitor cells. We show that the enhancer is accessible in multipotential cell chromatin but functionally incompetent before granulocyte commitment. Multipotential cells contain both Pu1 and C-EBP alpha as enhancer-binding activities. Pu1 is unphosphorylated in both multipotential and granulocyte-committed cells but is phosphorylated in B lymphocytes, raising the possibility that differential phosphorylation may play a role in specifying its lymphoid versus myeloid functions. C-EBP alpha exists as multiple phosphorylated forms in the nucleus of both multipotential and granulocyte-committed cells. C-EBP beta is unphosphorylated and cytoplasmically localized in multipotential cells but exists as a phosphorylated nuclear enhancer-binding activity in granulocyte-committed cells. Granulocyte colony-stimulating factor-induced granulocytic differentiation of multipotential progenitor cells results in activation of C-EBP delta expression and functional recruitment of C-EBP delta and C-EBP beta to the nucleus. Our results implicate Pu1 and the C-EBP family as critical regulators of myeloperoxidase gene expression and are consistent with a model in which a temporal exchange of C-EBP isoforms at the myeloperoxidase enhancer mediates the transition from a primed state in multipotential cells to a transcriptionally active configuration in promyelocytes.

Animals↗

PubMed1996

Properties of whole saliva and dental plaque in relation to 40-month consumption of chewing gums containing xylitol, sorbitol of sucrose.

Samples of whole saliva and dental plaque were collected from initially 10-year old subjects who participated in a 40-month cohort study investigating the effect of chewing gum usage on caries rates. The subjects represented nine cohorts of which one did not receive gum, while in eight cohorts the subjects received gum containing either xylitol, sorbitol, their mixtures, or sucrose as bulk sweeteners, the maximum sweetener consumption in the form of gums being up to 10.7 g/day, used in 3-5 daily chewing episodes. Gum usage had no significant effect on the levels of salivary protein, IgA, alpha-amylase, peroxidase, lysozyme, SCN and buffer capacity. At the endpoint, the group that received 100% xylitol pellet-shaped gum five times/day, had significantly lower levels of sucrase (p <0.05) and free sialic acid (p < 0.001) in whole saliva than at baseline. This group showed significantly (p <0.05) smaller plaque index scores at two cross-sectional measurements, and exhibited the lowest log(10) counts of salivary lactobacilli at endpoint than most other groups. The salivary levels of peptidase(s) (oligopeptidase B-like enzymes) hydrolyzing N-alpha-benzoyl-DL-arginyl-p-nitroaniline were significantly (p<0.05) or almost significantly lower in groups which received 100% xylitol pellet gums. All groups exhibited obviously an aging-related increase of salivary mutans streptococcus scores, except the above xylitol group in which the mean scores did not change.

Aniline Compounds↗

PubMed1996

Polyol chewing gums and caries rates in primary dentition: a 24-month cohort study.

The effect of 2-year chewing-gum use on the caries rates of primary teeth was studied in a combined school and home program in a sample of 510 initially 6-year-old subjects with high caries experience, low availability of fluoride, and difficult access to dental care. The gum, formed into either sticks or pellets, comprised either xylitol, sorbitol, or mixtures thereof. The gum was chewed for 5 min under supervision five times a day during the school year, and for variable times during nonschool days. Seven groups were studied. One group received no gum; two xylitol gum groups received either pellet or stick gum as did, two sorbitol gum groups, and two groups received either of two types of xylitol/sorbitol pellet gum. The response variable was the development of a frank carious lesion detectable by physical loss of enamel and probable extension to the dentin for those surfaces of primary teeth that were not cavitated at baseline. Caries rates associated with the use of each of the gum types were compared to the caries rates in the no-gum group. The usage of all polyol gums resulted in a significant decrease of the caries onset rate (p < 0.05). The caries onset risk for a primary surface in the xylitol pellet and the sorbitol pellet groups was 35 and 44% of that in the no-gum group (relative risk, 0.35; 95% confidence interval, 0.21-0.59; relative risk, 0.44; 95% confidence interval, 0.30-0.63, respectively). The caries onset risk in the xylitol stick gum group was 53% of that in the no-gum group (relative risk, 0.53; 95% confidence interval, 0.39-0.72), which was marginally (p = 0.1520) lower than in the sorbitol stick gum group (relative risk, 0.70; 95% confidence interval, 0.52-0.94). The usage of both xylitol/sorbitol mixtures in pellet form was associated with a caries onset rate comparable with the usage of the xylitol stick gum. The largest caries risk reduction was observed in the group receiving xylitol pellet gum.

Belize↗

PubMed1996

Hospital charges for stroke patients.

BACKGROUND AND PURPOSE: Stroke is a common disease with a yearly cost in the United States of approximately $30 billion. The increasing prevalence of managed care and cost-containment measures may affect the delivery of stroke care now and in the future. This study was performed to determine (1) hospital charges and test utilization for stroke patients and (2) the effectiveness of educational efforts in modifying test utilization and related hospital charges. METHODS: Patients with a diagnosis of stroke who were discharged from either the neurology service or another service of the Department of Medicine (DOM) were identified. Data on test utilization and hospital charges were collected and analyzed. Following this analysis, educational sessions were held in an effort to reduce the use of specific diagnostic tests. The effectiveness of these methods was studied in a second group of stroke patients. RESULTS: In the baseline period there were 303 stroke patients, of which 262 (86%) were discharged from the neurology service and 41 (14%) were discharged from other services of the DOM. Patients on the neurology service had a lower mean length of stay than patients on the other services of the DOM (9.2 days versus 10.5 days) and lower mean total charges per case ($13,149 versus $15,727), although the respective differences were not statistically significant. Patient on the neurology service were more likely to have both brain CT and MRI performed (82 of 262 patients, 31.3%) than patients on the other services of the DOM (4 of 41, 9.8%, P = .005). In addition, patients on the neurology service were more likely to undergo a transthoracic echocardiogram than patients on the other services of the DOM (71.8% versus 53.7%, P = .025). After educational sessions, the percentage of stroke patients on the neurology service having both CT and MRI fell from 31.3% to 17.7% (P = .005), and the number of stroke patients having a transthoracic echocardiogram fell from 71.8% to 60.3% (P = .025). However, the overall charges for stroke patients on the neurology services did not decrease. CONCLUSIONS: Education can be successful in reducing the utilization of and associated charges for specific diagnostic tests for some stroke patients. A multidisciplinary approach to case management, using tools such as care maps, may be necessary to realize significant cost savings in certain groups of stroke patients.

Aged↗

PubMed1995

Xylitol chewing gums and caries rates: a 40-month cohort study.

Dental caries is a pandemic infectious disease which can affect the quality of life and consumes considerable health care resources. The chewing of xylitol, sorbitol, and even sugar gum has been suggested to reduce caries rates. No clinical study has simultaneously investigated the effectiveness of these gums when compared with a group receiving no chewing gum. A 40-month double-blind cohort study on the relationship between the use of chewing gum and dental caries was performed in 1989-1993 in Belize, Central America. One thousand two hundred and seventy-seven subjects (mean age, 10.2 years) were assigned to nine treatment groups: one control group (no supervised gum use), four xylitol groups (range of supervised xylitol consumption: 4.3 to 9.0 g/day), two xylitol-sorbitol groups (range of supervised consumption of total polyols: 8.0 to 9.7 g/day), one sorbitol group (supervised consumption: 9.0 g/day). The gum use during school hours was supervised. Four calibrated dentists performed the caries registrations by means of a modified WHO procedure. The primary endpoint was the development of an unequivocal caries lesion on a non-cavitated tooth surface. Compared with the no-gum group, sucrose gum usage resulted in a marginal increase in the caries rate (relative risk, 1.20; 95% confidence interval,0.96 to 1.49; p = 0.1128). Sorbitol gum significantly reduced caries rates (relative risk 0.74; 95% confidence interval, 0.6 to 0.92 ; p = 0.0074). The four xylitol gums were most effective in reducing caries rates, the most effective agent being a 100% xylitol pellet gum (relative risk, 0.27; 95% confidence interval, 0.20 to 0.36; p = 0.0001). This gum was superior to any other gum (p < 0.01). The xylitol-sorbitol mixtures were less effective than xylitol, but they reduced caries rates significantly compared with the no-gum group. DMFS analyses were consistent with these conclusions. The results suggest that systematic usage of polyol-based chewing gums reduces caries rates in young subjects, with xylitol gums being more effective than sorbitol gums.

Belize↗

PubMed1995

Stabilisation of rampant caries: polyol gums and arrest of dentine caries in two long-term cohort studies in young subjects.

The purpose of this paper is to report clinical observations on the stabilisation of dentine caries in two chewing gum studies carried out in young subjects. One study focused on the permanent dentition of 1,277 initially 10-year old subjects, while the other study was carried out on 510 initially 6-year old subjects and focused on the primary dentition. In both trials, several chewing gum formulas containing dietary polyols (xylitol and sorbitol, or their combinations) were used for up to 40 months (10-year olds) or up to 24 months (6-year olds). The daily consumption level of both polyols was up to 10.7 g per subject, used normally in 5-minute chewing episodes 3 to 5 times per day. Supervised chewing in schools lasted 5 min per episode, and for variable times during non-school days. Rehardening of dentine caries lesions was observed clinically by experienced, blinded examiners using sharp dental explorers and fibre optic light. After 40 months (permanent dentition) or after 18 months (primary dentition), rehardening (caries arrest) generally occurred more frequently in subjects who used polyol gums than in subjects who did not receive gum as part of the programmes, or who received sucrose gum. Arrest or non-progression of dentine caries was most frequently observed in subjects who used 100 per cent xylitol gums or mixtures of xylitol and sorbitol, but the differences between gums were not consistently significant. However, the usage of 100 per cent xylitol pellet-shaped gum was more frequently associated with arrest of dentine caries than other treatments. These results and previous studies suggest that high-xylitol chewing gum usage can retard or arrest even rampant dentine caries in conditions where effective restoration and prevention programmes have not been instituted, and can also provide additional protection against further caries development during full implementation of restorative procedures by holding the lesion in a non-progressive condition.

Belize↗

PubMed1994

A myeloid-lineage-specific enhancer upstream of the mouse myeloperoxidase (MPO) gene.

The myeloperoxidase (MPO) gene is selectively expressed during haemopoiesis in the granulocytic lineage. Compared with the erythroid (beta-globin) and B-cell (immunoglobulin) lineages, little is known of the regulatory sequences and transcription factors involved in the regulation of genes specific for granulopoiesis. We have approached this issue by identifying a strong enhancer for the murine MPO gene. A candidate enhancer region was mapped by the detection of a strong DNase I hypersensitive site, -3.4 to -3.2 kb upstream of the MPO gene. A 301 bp fragment encompassing the DNase I site was shown to have strong enhancer function in a transient assay following transfection of a reporter gene into a MPO-expressing cell (WEHI 3BD+), but was inactive in lymphoid cells. Analysis of sub-fragments revealed that the whole 301 bp fragment is required for maximal enhancer function.

Animals↗

PubMed1992

Circulating stem cells in mice treated with cyclophosphamide.

Chemotherapy has been used clinically to mobilize hematopoietic progenitor cells into the peripheral blood so that they can be harvested for autologous transplantation. In humans, this is demonstrated by the presence of circulating granulocyte-macrophage colony-forming cells (CFU-GM) and CD34-positive cells, but it has not been possible to confirm the presence of marrow-repopulating stem cells. In this study, we treated mice with 200 mg/kg cyclophosphamide (CY) and measured the numbers of white blood cells, day 12 CFU-S (CFU-S12), and CFU-GM in the peripheral blood. There was a peak in the numbers of CFU-S12 and CFU-GM 8 days after treatment with cyclophosphamide. Peripheral blood cells taken at this time rescued lethally irradiated mice and engraftment of donor cells was confirmed after 140 days in sex mismatched recipients using a Y chromosome-specific probe. In vitro culture of the blood cells harvested after cyclophosphamide showed that they proliferated in suspension cultures for at least a year in the presence of interleukin-3. The cultured cells rapidly lost their abilities to rescue irradiated mice and to form colonies in vitro, but they did not become leukemic. Also, CY-treated mice were irradiated with a leukemogenic dose of x-rays to coincide with peak circulating cell numbers but these animals did not develop an excess of leukemias over mice given irradiation alone.

Animals↗

PubMed1992

Immunoglobulin heavy-chain and CD3 delta-chain gene enhancers are DNase I-hypersensitive in hemopoietic progenitor cells.

Multipotential interleukin 3-dependent non-immortalized murine hemopoietic progenitor cells have DNase I-hypersensitive sites in the immunoglobulin heavy-chain and CD3 delta enhancers and transcribe germ-line T-cell antigen receptor gamma-chain (TCR gamma), but not IgM or TCR beta, genes. Induction of myeloid differentiation in these cells clones down expression and/or transcriptional accessibility of the immunoglobulin heavy-chain and TCR gamma genes. The CD3 delta enhancer region remains DNase I-hypersensitive but closes down in B cells. In embryonic stem cells and pan-mesodermal cells, these genes or enhancer regions are neither expressed nor DNase I-hypersensitive. These data suggest that lineage potential may be programmed, at least in part, by alterations in the accessibility or conformation of regulatory regions of genes and that some promiscuity of gene expression and/or accessibility can precede lineage commitment and maturation in progenitor cells induced to self-renew by interleukin 3.

Animals↗

PubMed1992

Multilineage phenotypes of interleukin-3-dependent progenitor cells.

Interleukin-3 (IL-3)-dependent murine FDCP-mix cells have multilineage differentiation capacity; they are nonleukemic, have a normal karyotype, and are nonimmortalized. These cells coexpress on their cell surface the "early" B-lineage marker B220/CD45R and the myeloid marker Mac-1/iC3b receptor (CR3), transcribe germline T-cell receptor gamma genes, and express the macrophage lineage growth factor receptor gene c-fms as a predominant 8.4-kb transcript. They do not detectably express at the stable mRNA or protein level other lymphoid precursor cell genes including CD2, TdT, lambda 5, and BP1. Induction of granulocyte/macrophage differentiation in these cells closes down expression of the lymphoid genes and activates stable expression of genes specific to the myeloid lineage, including myeloperoxidase. Expression of the c-fms gene at the mRNA level is upregulated and the dominant stable transcript is now in the 4.1-kb form typical of the macrophage lineage. These data provide a plausible explanation for the coexpression of lymphoid and myeloid lineage markers on human leukemic cells of stem cell or progenitor cell origin and have implications for the programming of lineage potential in normal multipotential hematopoiteic progenitor cells.

Animals↗