Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin beta3”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,063 records · Page 59Linked to original sources
PubMed2003

Cell-to-cell variability in the differentiation program of human megakaryocytes.

Differentiation of CD34(+) stem/progenitor cells into megakaryocytes is thought to be a uniform, unidirectional process, in which cells transform step by step from less differentiated precursor stages to more differentiated megakaryocytes. Here we propose the concept and present evidence based on single-cell analysis that differentiation occurs along multiple, partially asynchronous routes. In all CD34(+) cells cultured with thrombopoietin, surface appearance of glycoprotein IIIa (GPIIIa) preceded that of GPIb, indicating that the expression of these glycoproteins occurs in a timely ordered manner. Cellular F-actin content increased in parallel with GPIb expression. Only cells that expressed GPIb were polyploid, pointing to co-regulation of GPIb expression, actin cytoskeleton formation and polyploidization during megakaryocytopoiesis. On the other hand, most progenitor cells responded to thrombin but not to thromboxane A(2) analogue by rises in cytosolic [Ca(2+)](i). The appearance of thromboxane-induced responses during megakaryocytopoiesis was not strictly linked to glycoprotein expression, because cells showed responsiveness either before or after GPIb expression. The same non-strictly sequential pattern was observed for disappearance of the Ca(2+) response by prostacyclin mimetic; in some megakaryocytes it occurred before and in others after GPIb expression. Thus, megakaryocytic differentiation follows along independent routes that are either strictly sequential (GPIIIa and GPIb expression) or proceed at different velocities (Ca(2+) signal regulation).

Antigens, CD34↗
PubMed2004

Direct demonstration of involvement of the adaptor protein ShcA in the regulation of Ca2+-induced platelet aggregation.

Platelet aggregation is mediated by conformational change of integrin alpha(IIb)beta(3). Tyrosine-phosphorylation of cytoplasmic domain of beta(3) upon platelet activation has been demonstrated to play a critical role in this process. Recently, the adaptor protein ShcA has been shown to bind to the tyrosine-phosphorylated beta(3), while it remains open whether ShcA plays any role in platelet aggregation. Here, we show that ShcA bound to tyrosine-phosphorylated beta(3)-tail peptide through its phosphotyrosine-binding domain in vitro. Then, we examined the involvement of ShcA in platelet aggregation by a previously established in vitro assay using platelets permeabilized with streptolysin-O, where exogenous addition of platelet cytosol is required for reconstitution of the Ca(2+)-induced aggregation. When ShcA was specifically depleted with anti-ShcA antibody from the cytosol, this ShcA-depleted cytosol lost the aggregation-supporting activity, which was rescued by addition of purified recombinant ShcA. Thus, ShcA is essential for the Ca(2+)-induced platelet aggregation.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Megakaryocytes modulate osteoblast synthesis of type-l collagen, osteoprotegerin, and RANKL.

We have previously reported evidence that megakaryocytes may play a role in bone remodeling, possibly by interactions with cells at the bone surface. To investigate the direct effects of megakaryocytes on osteoblasts, maturing megakaryocytes (CD61 positive cells) were isolated and added to cultures of human osteoblasts. Osteoblasts alone and osteoblasts treated with CD61-negative (non-megakaryocytic) cells were used as control cultures. After 48 h in culture, megakaryocytes were removed and osteoblasts immunolocalized for type-1 collagen, osteoprotegerin (OPG), and RANKL expression. Similar cultures were used for RNA extraction with mRNA for Col 1A1, OPG, and RANKL in osteoblasts measured quantitatively by RT-PCR. Osteoblasts cultured alone showed high levels of expression of collagen with 74% (+/-7) of cells staining positively. When cultured with megakaryocytes, the number of positively staining cells remained similar but the intensity of expression was increased 1.54-fold (P < 0.02). OPG was expressed by 32% (+/-6.3) of osteoblasts increasing to 51% (+/-5.5) when cultured in the presence of megakaryocytes (P < 0.01) with a 1.63-fold increase in intensity of expression (P < 0.01). In contrast, osteoblasts cultured with megakaryocytes showed suppression of RANKL expression; 35.6% (+/-5.8) of osteoblasts cultured alone stained positively decreasing to 24.3% (+/-5.3) with a 1.6-fold diminished intensity of expression (P < 0.02). Osteoblasts co-cultured with CD61-negative cells showed no differences in collagen, OPG, or RANKL expression levels compared to osteoblasts cultured alone. mRNA data supported these findings with a 3.1-fold increase in Col 1A1 expression in megakaryocyte-treated cultures compared to controls (P < 0.02). Low-level OPG mRNA expression increased 8.14-fold in osteoblasts cultured in the presence of megakaryocytes (P < 0.01), while RANKL expression was suppressed 3.3-fold (P < 0.02). These results demonstrate that in vitro, megakaryocytes have direct effects on osteoblastic production of factors affecting both bone formation and resorption. These data provide further evidence that megakaryocytes may play an important role in bone remodeling.

Antigens, CD34↗
PubMed2006

Osteoclast formation and bone resorption are inhibited by megakaryocytes.

It has been previously reported that addition of megakaryocytes (MKs) to osteoblasts in vitro results in increased osteoblastic collagen and osteoprotegerin (OPG) production, suggesting a role for MKs in bone formation. To further investigate this role, we have studied the effects of MKs on osteoclast formation and activity. Human osteoclasts were generated from CD14 monocytes isolated from peripheral blood and cultured in the presence of M-CSF and sRANKL on dentine and calcium phosphate substrates. MKs were generated from CD34+ cells isolated from either human peripheral blood or cord blood and cultured in liquid medium for 6 days, after which time maturing MKs (CD61-positive cells) were isolated and added to monocyte cultures. After 6 and 9 days of culture, the number of osteoclasts identified morphologically and by TRAP staining was counted. Cells were removed and the area of resorption was identified by von Kossa staining and quantitatively assessed by image analysis. The addition of MKs to osteoclast cultures at day 0 inhibited the number of osteoclasts formed 1.9-fold (p>0.003), whereas addition at 3 days had no effect on osteoclast number. The presence of MKs inhibited resorption 8.7-fold when co-cultured with osteoclasts from day 0 (p>0.004), but only by 3.1-fold when co-cultured from day 3 (p>0.01). In dose-response experiments, it was found that 1-10% of MKs added to monocyte cultures elicited the greatest inhibition of resorption. Similar osteoclast cultures were treated with CD61-negative cells (non-MKs) to confirm that the inhibition of osteoclast formation and activity was specifically due to MKs. Experiments with a cell-impermeable membrane indicated that both cell to cell contact and release of soluble factor(s) were involved in mediating these effects. These results show that MKs inhibit osteoclast formation and activity. The most pronounced effects were seen when MKs and osteoclasts were co-cultured from day 0, suggesting that MKs act primarily on osteoclast precursors.

Antigens, CD34↗
PubMedDate not supplied

Thrombotic thrombocytopenic purpura causing rapid unexpected death: value of CD61 immunohistochemical staining in diagnosis.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) shares histologic features with disseminated intravascular coagulation (DIC) but is clinically distinct. TTP may result in myocardial hemorrhages and rapid death. We compared rapidly fatal TTP with heart involvement and DIC cases to determine if the differential diagnosis of TTP and DIC could be aided by immunohistochemical techniques. DESIGN: We examined 11 hearts from seven women and four men dying with TTP (aged 34+/-10 years) and 8 hearts from patients dying with DIC (five women, three men, aged 58+/-16 years). The diagnosis of TTP was established on histologic findings and identification of thrombocytopenia with schistocytes on premortem blood smear. Underlying conditions for TTP were recent diarrheal illness (3), autoimmune disease (3), sickle cell disease, HIV infection, cocaine abuse, and none known (2). Underlying conditions for DIC were disseminated carcinoma (4), multiorgan failure after open-heart surgery (2), pancreatitis (1), and placental abruption (1). Antibodies against platelet glycoprotein IIIa (CD61) and fibrin II were applied to formalin fixed tissue sections and detected by the avidin biotin techniques, and platelet and fibrin capillary thrombi were quantitated. RESULTS: Gross myocardial hemorrhages were present in 7/11 cases of TTP and 0 cases of DIC (P<.001). Capillary thrombi were present in all cases by routine histologic techniques but were often difficult to discern. Platelet thrombi were strongly highlighted by stains for CD61 and seen at a density of 8.0+/-3.1/mm(2) in TTP versus 0.5+/-0.4/mm(2) in DIC (P=.0001). In TTP, there were 12.1+/-5.9/mm(2) fibrin capillary thrombi and 4.8+/-5.8/mm(2) in DIC (P=.05). CONCLUSION: In the myocardium, rapidly fatal TTP is characterized by the diffuse presence of intracapillary platelet-rich thrombi, in contrast to DIC, which is characterized by predominantly fibrin thrombi. Immunohistochemical staining for CD61 and fibrin II is helpful in diagnosing TTP and distinguishing it from DIC.

Adult↗
PubMed2006

Platelet glycoprotein polymorphisms: risk, in vivo expression and severity of atherothrombotic stroke in Chinese.

BACKGROUND: Polymorphisms in platelet glycoprotein (GP) receptors Ia, Ib and IIIa may be heritable risk factors for platelet-dependent thrombosis leading to death. The precipitation of stroke by occlusive thrombi has led to the investigation of the platelet surface GP receptors, that are involved in critical steps in the activation of platelets. Three polymorphisms in the GP Iba gene and one in each of GPIIIa, GP Ia were selected based on the evidence of functional effects on structure or expression as candidates for risk. We also determined whether these polymorphisms were associated with in vivo expression levels of platelet GP receptors and the severity of the neurological deficit. METHODS: A Chinese hospital-based case-control study was conducted with 119 cases of atherothrombotic stroke and 166 age and sex matched controls. Genotyping was performed on lymphocyte DNA by standard methods and platelet GP expression levels were measured by flow-cytometry. RESULTS: Allele and genotype frequencies of the GP receptor polymorphisms differ considerably between ethnic populations. We found the D allele of the GP Iba VNTR polymorphism was significantly associated with atherothrombotic stroke in our Chinese cohort, however we did not find a relationship among these polymorphisms, the expression levels of GP receptors and severity of the neurological deficit. CONCLUSIONS: In our Chinese cohort the D allele of the GP Iba VNTR polymorphism is associated with atherothrombotic stroke. The number of VNTR repeats alters the length of amino acid sequence, which might affect the structure and function of this receptor.

Adult↗
PubMed2005

Downregulation of vascular endothelial growth factor and integrinbeta3 by endostatin in a mouse model of retinal neovascularization.

Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and integrinbeta3 in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 microg endostatin at P12. At P17, retinal VEGF and integrinbeta3 mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice (p<0.01) and a 2.5-fold decrease in integrinbeta3 levels between hyperoxia mice and endostatin-treated mice (p<0.01). These data suggest that intraocular expression of VEGF and integrinbeta3 mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization.

Angiogenesis Inhibitors↗
PubMed2006

Shedding of procoagulant microparticles from unstimulated platelets by integrin-mediated destabilization of actin cytoskeleton.

Platelet activation by potent, Ca(2+)-mobilizing agonists results in shedding of microparticles that are active in coagulation. Here we show that platelets under storage produce procoagulant microparticles in the absence of agonist. Microparticle formation by resting platelets results from alphaIIbbeta3 signaling to destabilization of the actin cytoskeleton in the absence of calpain activation. Integrin-mediated spreading of platelets over fibrinogen similarly results in microparticle formation. After transfusion of stored platelet preparations to thrombocytopenic patients, the microparticles contribute to coagulant activity in vivo.

Actin Cytoskeleton↗
PubMed2005

The antiprogesterone Org 31710 inhibits human blastocyst-endometrial interactions in vitro.

OBJECTIVE: To investigate the effect of the anti-P Org 31710 on human blastocyst attachment to cultured endometrial epithelial cells. DESIGN: Experimental in vitro study. SETTING: University hospital. PATIENT(S): Eleven fertile endometrial donors. INTERVENTION(S): Timed endometrial biopsy for cell cultures. MAIN OUTCOME MEASURE(S): Blastocyst attachment rate on endometrial cell cultures; secretion of glycodelin and leukemia inhibitory factor into the culture medium measured by RIA and ELISA techniques; and expression of progesterone receptors, interleukin-1 receptor type-1, and integrin subunit beta(3) on endometrial epithelial cells examined by immunohistochemistry. Endometrial pinopodes visualized by scanning electron microscopy. RESULT(S): Eleven of 16 human blastocysts attached to control cultures, whereas none of 10 blastocysts attached when Org 31710 was added to the culture medium (P=.0007). Immunohistochemical studies demonstrated no significant differences between groups. Biochemical analyses displayed a trend toward higher glycodelin secretions and, by scanning electron microscopy, a tendency toward less pinopode formation in the Org 31710 group, but the results did not reach statistical significance. The presence of swollen microvilli, precursors of endometrial pinopodes, was significantly reduced on cultures with Org 31710 (P=.03). CONCLUSION(S): The study presents a model for human blastocyst-endometrial interactions responding to an anti-P drug. The exact mechanism for the anti-attachment properties of Org 31710 on the cultured endometrial cells and the blastocysts needs further evaluations.

Blastocyst↗
PubMed2005

Association of PLA2 polymorphism of the ITGB3 gene with early fetal loss.

To study the association between early fetal loss and the presence of the PLA2 polymorphism of the ITGB3 gene we conducted a case-control study on 98 cases (i.e., women in fertile age, who experienced at least one episode of early fetal loss) and 38 healthy controls. PLA2 polymorphism was present in 44.2% of cases and 18.4% of controls, and cases with one (n = 24) event had an odds ratio (OR) = 2.7 (95% confidence interval [CI] 0.7-10.0), with two events (n = 52) an OR = 3.8 (95% CI 1.3-11.5), and with three (n = 16) or four abortions (n = 6) had a combined OR = 4.4 (95% CI 1.2-17.0), compared to controls, indicating that PLA2 polymorphism may be implicated in an inherited form of thrombophilia, and to early fetal loss.

Abortion, Spontaneous↗
PubMed2004

Platelet GPIaC807T polymorphism is associated with negative outcome of sudden hearing loss.

To determine the relevance of inherited prothrombotic risk factors in sudden hearing loss, we investigated 85 patients with sudden hearing loss of >/= 60 dB for the presence of inherited prothrombotic risk factors. The FV G1691A, FII G20210A, GPIa C807T, GPIIIa PIA1/A2, PAI-1 4G/5G, t-PA Alu repeat ID, MTHFR C677T and CBS 844ins68 genotypes were investigated. Allele frequencies found in patients were compared to those of 85 healthy control subjects of the same ethnic background using Chi-squared and odds-ratio analysis. The frequency of the GPIa807T allele was significantly elevated in patients compared to controls. In addition, allele frequency and genotype distribution of GPIa was significantly elevated in the patient group without recovery after 3 months of sudden hearing loss onset. Allele frequencies of all other prothrombotic risk factors investigated here did not differ from those of the control subjects. The single-nucleotide polymorphism of GPIa C807T seems to play a role as a prognostic factor in recovery from sudden hearing loss.

Adolescent↗
PubMed2005

Renin-angiotensin system and haemostasis gene polymorphisms and outcome after coronary artery bypass graft surgery.

BACKGROUND: Coronary artery bypass graft surgery is associated with a considerable 2-year mortality rate. Gene polymorphisms of the renin-angiotensin system may be associated with the risk of hypertension and cardiovascular disease. The angiotensin I-converting enzyme DD genotype has recently been identified as independent predictor of the outcome after coronary artery bypass graft surgery. Genetic factors of the clotting system may be related to the risk of myocardial infarction and restenosis after coronary interventions. The aims of the present study were to investigate whether gene polymorphisms of the renin-angiotensin system (angiotensinogen 235 M/T, angiotensin II type 1 receptor 1166 A/C) or the clotting system (glycoprotein IIIa PlA1/PlA2 and factor V Leiden 1691 G/A) are associated with the outcome after coronary artery bypass grafting. METHODS: A study population of 247 patients was followed-up 2 years after coronary artery bypass graft surgery. The primary end-point was total mortality. The secondary end-point was mortality from cardiac cause or the need for myocardial revascularization (percutaneous coronary interventions or recurrent surgery) during follow-up. Geno typing was performed by polymerase chain reaction- and restriction fragment length polymorphism-based techniques. RESULTS: An older age and the non-use of the internal mammary artery graft were identified as independent predictors of the primary end-point after coronary artery bypass grafting. A decreased left ventricular ejection fraction was an independent predictor for the secondary end-point. No association was found between any of the genetic factors and the outcomes after coronary artery bypass graft surgery in the main factor regression models. However, the angiotensin II type 1 receptor 1166 A/C gene polymorphism modulated the effects of age on the primary end-point, and the angiotensinogen 235 M/T gene polymorphism modulated the effects of age on the secondary end-point. CONCLUSION: We conclude that there are interactions between the angiotensin II type 1 receptor 1166 A/C as well as the angiotensinogen 235 M/T gene polymorphism and age with respect to the outcome after coronary artery bypass graft surgery. The glycoprotein IIIa PlA1/PlA2 and the factor V Leiden 1691 G/A gene polymorphisms were not associated with mid-term mortality or cardiac morbidity after coronary artery bypass grafting.

Adult↗
PubMed2005

Real-time quantitative PCR assay for analysis of platelet glycoprotein IIIa gene expression.

A quantitative detection assay for analysis of platelet glycoprotein GPIIIa gene expression is presented. The assay uses two fluorescently labeled TaqMan MGB probes to detect the polymorphic site in GPIIIa nucleotide sequence, leading to antigens HPA-1a and HPA-1b. In order to avoid the influence of DNA contamination on RNA quantification, a forward primer was constructed to span an exon-exon junction. The assay is therefore applicable to expression studies also in samples containing only a small amount of contaminating DNA. To standardize the amount of sample cDNA added to the reaction, amplification of endogenous control 18SrRNA was included in a separate well. The amplification validation experiment showed a high real-time PCR efficiency for HPA-1a, HPA-1b and 18SrRNA. Relative quantification was therefore performed using the comparative C(T) method. The assay was optimized on a reversely transcribed total RNA from platelets, and the specificity rate was determined by sequencing. The amount of cDNA at which amplification was still clearly detectable was 5 ng. This newly developed real-time quantitative PCR assay is a sensitive, reproducible and reliable method. It is suitable for studying different stages of megakaryopoiesis, monitoring molecular alteration in defective platelets and determining differences in the GPIIIa expression level between normal and pathological megakaryocytic differentiation pathways.

Antigens, Human Platelet↗
PubMed2004

Platelet glycoprotein Ia C807T, Ib C3550T, and IIIa Pl(A1/A2) polymorphisms and ischemic stroke in young Taiwanese.

Platelet plays a pivotal role in the pathogenesis of thrombotic cardiovascular diseases. Recently, the polymorphism of platelet glycoprotein (GP) genes has been reported to be associated with an increased risk for ischemic stroke. The purpose of this study is to evaluate the association between platelet GP genetic variants and ischemic stroke in young Taiwanese. We conducted a case-control study in 157 young ischemic stroke patients recruited between September 2001 and March 2003 and 157 age- and sex-matched controls. The genotypes of platelet GP Ia C807T, GP Ib C3550T, and GP IIIa Pl(A1/A2) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Student's t-test, chi-square test, and logistic regression modeling were used for data analyses. The GP Ia C807T CC, CT and TT genotype frequencies were similar between patients (50.3%, 43.9%, 5.7%) and controls (53.5%, 38.9%, 7.6%; p=0.58). There were no significant differences in GP Ib C3550T CC and CT genotype distributions between patients (91.1%, 8.9%) and controls (91.7%, 8.3%; p=0.84). Of all subjects, none carries GP IIIa Pl(A2) mutation. In conclusion, platelet GP Ia C807T and GP Ib C3550T polymorphisms in our population are less common compared with Caucasians, and GP IIIa Pl(A1/A2) genetic mutation is not found, and all of them are not associated with ischemic stroke in young Taiwanese.

Adolescent↗
PubMed2004

Genetic polymorphisms associated with thrombophilia and vascular disease in women with unexplained late intrauterine fetal death: a multicenter study.

OBJECTIVE: We determined whether gene polymorphisms associated with thrombophilia and vascular disease as etiologic factors were involved in the pathogenesis of pregnancy-associated complications. METHODS: We conducted a multicenter case-control study in which we studied 94 women with late unexplained intrauterine fetal death (IUFD) and 94 healthy women with at least one uncomplicated full-term pregnancy and no history of IUFD. We obtained blood samples from all subjects and analyzed their DNA for 12 common polymorphisms of thrombophilic and vascular genes (factor V Leiden, factor V H1299R, prothrombin G20210A, factor XIII V34L, MTHFR C677T, MTHFR A1298C, beta-fibrinogen-455 G to A, PAI-1 4G/5G, GPIIIa L33P, HFE C282Y, apolipoprotein B R3500Q, and apolipoprotein E2/E3/E4). RESULTS: We found no significant association between any of the polymorphisms investigated and IUFD. Subgroup analyses involving various combinations of polymorphisms and in which gestational age and fetal weight were corrected for also showed no significant results. CONCLUSIONS: Our data represent the largest study to date with respect to thrombophilic and vascular gene polymorphisms in IUFD. In accordance with others, we challenge the importance of thrombophilic and vascular gene polymorphisms in the pathogenesis of this condition.

Adult↗
PubMed2005

Prediction of the excessive perioperative bleeding in patients undergoing coronary artery bypass grafting: role of aspirin and platelet glycoprotein IIIa polymorphism.

OBJECTIVE: The presence of the glycoprotein IIIa allele PlA2 is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin, which could favor coronary thrombosis. We wondered whether PlA1/A2 genetic polymorphism could affect the postoperative bleeding in patients undergoing coronary artery bypass grafting. We also aimed to assess the effects of aspirin pretreatment and to ascertain the value of platelet function studies as predictors of postoperative bleeding. METHODS: In a randomized, double-blind study, patients undergoing coronary artery bypass grafting were pretreated with a 150-mg dose of aspirin orally 12 and 3 hours before surgery (n = 51, 41 elective) or with placebo (n = 51, 43 elective). The hemostasis was monitored by Simplate (bioMérieux, Inc, Durham, NC) bleeding time and capillary closure time (platelet function analyzer PFA 100; Sysmex UK Ltd, Milton Keynes, United Kingdom). Postoperative bleeding and blood products transfusions were recorded. The glycoprotein IIIa polymorphism was analyzed. RESULTS: Bleeding was significantly greater in PlA1 homozygotes from control group. Blood loss was significantly greater (by 25%) in aspirin group. The volume of blood products transfusions in aspirin patients was significantly larger (by 137%). When subjects were stratified accordingly to blood platelet glycoprotein IIb/IIIa genotype, in the aspirin group PlA2 carriers had greater blood loss than PlA1 homozygotes (1858 +/- 932 mL vs 1216 +/- 525 mL, P < .05). CONCLUSION: PlA1 homozygotes normally had a greater risk of perioperative bleeding. Capillary closure time had no advantage relative to Simplate bleeding time in predicting postoperative blood loss. Aspirin pretreatment revealed no beneficial effects and resulted in increased postoperative bleeding and requirement for blood product transfusions after coronary artery bypass grafting in patients with stable angina. It was most unfavorable for PlA2 carriers.

Alleles↗
PubMed2005

Histologic and molecular characterizations of megakaryocytic leukemia in mice.

Six cases of megakaryocytic leukemia (MKL) were identified and analyzed for morphology and molecular features. MKL were composed of megakaryocyte lineage cells ranging from immature to quite mature cells. VWF, GATA1 and RUNX1 were strongly expressed in megakaryocytes in both normal spleen and MKL as analyzed by immunohistochemistry (IHC). Altered expression of Meis1, Pbx1 and Psen2 and Lef1 in MKL detected with oligonucleotide microarrays was confirmed by qPCR and IHC. This is the first report of spontaneous MKL in mice, defining VWF as a biomarker for diagnosis and suggesting possible involvement of a series of genes in disease pathogenesis.

Animals↗