http://www.ehoonline.org The latest research articles published by Experimental Hematology & Oncology 2013-06-06T00:00:00Z Background: Tumor development is recently hypothesized to depend on a rare cell population with stem cell properties, such cells are called cancer stem cells (CSCs) or tumor-initiating cells (TICs). From various cancer tissues or cancer cell lines, CD133 expressing cells were found to define a unique CSC/TIC phenotype. To study whether that also could be the case in lung cancer, we examined different lung cancer cell lines for CD133 expression. Results: Among the 4 cell lines studied, only the cell line LC-42 expressed CD133. Therefore, LC-42 was further characterized and studied with special emphasis on identifying the presence of CD133+ CSCs/TICs. FACS sorted CD133high and CD133dim subpopulations from LC-42 showed no differences in soft agar colony-forming capacity and spheres-forming capacity in serum-free cultures. LC-42 cells contained Side Population (SP), and only SP cells were able to form spheres. Furthermore, Nanog expression was significantly higher in SP than in non-SP. However, no difference was observed of CD133 expression in SP and non-SP. When CD133high and CD133dim cells were serially xeno-transplanted in NOD/SCID mice, both formed tumours similar to their parental LC-42 cells. There were no expression differences for NANOG, OCT4 and SOX2 examined immunohistochemically in the xenografts from both cell fractions. Conclusion: Our data do not show a difference in tumorigenic potential of CD133high and CD133dim cells with respect to any of the parameters analyzed in vitro and in vivo, suggesting that CD133 expression is not restricted to cancer-initiating cells in the human lung cancer cell line LC-42. http://www.ehoonline.org/content/2/1/16 Ping Wang Zhenhe Suo Mengyu Wang Hanne Høifødt Øystein Fodstad Gustav Gaudernack Gunnar Kvalheim Experimental Hematology & Oncology 2013, null:16 2013-06-06T00:00:00Z doi:10.1186/2162-3619-2-16 /content/figures/2162-3619-2-16-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 16 2013-06-06T00:00:00Z PDF Tumor-associated antigens (TAAs) recognized by cellular and/or humoral effectors of the immune system are attractive targets for diagnostic and therapeutic approaches to human cancer. Different approaches can be used to comprehensively characterize and validate the identified TAA/anti-TAA systems, which are potential biomarkers in cancer immunodiagnosis. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The high fatality rate of HCC within one year after its detection might be partly attributed to a lack of diagnostic methods that enable the early detection. Our previous studies have shown that novel autoantibodies can appear which are not detected prior to pre-malignant conditions during transition from chronic liver disease to HCC. The hypothesis we advance is the transition to malignancy can be associated with autoantibody response to certain cellular proteins that might have some role in tumorigenesis. We propose that the information that the cancer patient’s immune system is conveying in the form of autoantibodies to tumor-associated antigens (TAAs) should be utilized to a greater extent in identifying early signs of tumorigenesis. In this review, we will focus on the important features of TAA and the possibility that autoantibodies to TAAs can be used as biomarkers in immunodiagnosis and prognosis of HCC. http://www.ehoonline.org/content/2/1/15 Liping Dai Ningjing Lei Mei Liu Jian-Ying Zhang Experimental Hematology & Oncology 2013, null:15 2013-05-20T00:00:00Z doi:10.1186/2162-3619-2-15 /content/figures/2162-3619-2-15-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 15 2013-05-20T00:00:00Z XML γδ T lymphocytes play an important role in immune reactions towards infections and malignancies. In particular, Vγ9–Vδ1+ T lymphocytes are thought to play protective antiviral roles in human CMV infection. Recently, Vδ1+ T lymphocytes were proposed to also have anti- B-CLL reactivity. Here we report a case of 48-year-old man who received allogeneic stem cell transplantation for progressive B-CLL. Within one year after transplantation, lymphoma relapsed despite a dramatic increase of Vδ1+ T cells in the patient’s blood. In vitro killing assays revealed activity of patient’s γδ cells against CMV target cells, but not against the relapsing lymphoma-cells. This argues for a contribution of Vδ1+ cells in the immune reaction against CMV reactivation, but does not support a strong correlation of expanded Vδ1+ T cells and favorable disease outcome in B-CLL patients. http://www.ehoonline.org/content/2/1/14 Immo Prinz Kristina Thamm Matthias Port Eva Weissinger Michael Stadler Ildar Gabaev Roland Jacobs Arnold Ganser Christian Koenecke Experimental Hematology & Oncology 2013, null:14 2013-05-11T00:00:00Z doi:10.1186/2162-3619-2-14 /content/figures/2162-3619-2-14-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 14 2013-05-11T00:00:00Z XML Cardiac metastasis of germ cell tumors is extremely rare, particularly in females. We report a case of a 26-year-old previously healthy woman who presented with a 5-month history of abdominal pain, weight loss, fever, generalized lymphadenopathy, and acanthosis nigricans. Biopsy of cervical lymph nodes revealed a poorly differentiated neoplasm. Immunohistochemical staining was positive for alpha-fetoprotein suggesting the diagnosis of a germ cell tumor. During the investigation, the patient developed heart failure and a mass attached to the right ventricle was detected by the echocardiogram. In a few days, she developed multiple organ failure and died. Post-mortem examination revealed a malignant mixed germ cell tumor of the right ovary with extensive hematogenic and lymphatic dissemination, a polypoid mass attached to the right ventricle, emboli in the endocardial and epicardial vessels, and infiltration surrounding the coronary arteries. To the best of our knowledge this is the third report of grossly visible heart metastases from a yolk sac tumor in a female patient. A summary of all published cases of germ cell tumors with cardiac metastasis over the last 20 years is also presented. http://www.ehoonline.org/content/2/1/13 Maria Carmo Pereira Nunes Daniel Moreira Teresa Cristina Abreu Ferrari Experimental Hematology & Oncology 2013, null:13 2013-04-30T00:00:00Z doi:10.1186/2162-3619-2-13 /content/figures/2162-3619-2-13-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 13 2013-04-30T00:00:00Z XML Activation of plasminogen on the cell surface initiates a cascade of protease activity with important implications for several physiological and pathological events. In particular, components of the plasminogen system participate in tumor growth, invasion and metastasis. Plasminogen receptors are in fact expressed on the cell surface of most tumors, and their expression frequently correlates with cancer diagnosis, survival and prognosis. Notably, they can trigger multiple specific immune responses in cancer patients, highlighting their role as tumor-associated antigens. In this review, three of the most characterized plasminogen receptors involved in tumorigenesis, namely Annexin 2 (ANX2), Cytokeratin 8 (CK8) and alpha-Enolase (ENOA), are analyzed to ascertain an overall view of their role in the most common cancers. This analysis emphasizes the possibility of delineating new personalized therapeutic strategies to counteract tumor growth and metastasis by targeting plasminogen receptors, as well as their potential application as cancer predictors. http://www.ehoonline.org/content/2/1/12 Patrizia Ceruti Moitza Principe Michela Capello Paola Cappello Francesco Novelli Experimental Hematology & Oncology 2013, null:12 2013-04-17T00:00:00Z doi:10.1186/2162-3619-2-12 /content/figures/2162-3619-2-12-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 12 2013-04-17T00:00:00Z XML Background: Relapsed T-lineage acute lymphoblastic leukemia (T-ALL) has been an incurable disease. Recent reports showed that an L-arginine depleting enzyme, pegylated arginase (BCT-100) may be effective against T-ALL cells. On the other hand, studies including ours had shown the symbiosis of ALL blasts and human mesenchymal stromal cells (hMSCs) in bone marrow microenvironment during L-asparaginase treatment. As L-asparaginase and BCT-100 both act by depleting lymphoid cells of specific amino acid, we hypothesized that hMSCs may also protect T-ALL blasts from BCT-100 treatment in co-culture and such protection may be abrogated by pre-treating hMSCs with vincristine (VCR). Methods: XTT assay was used to test sensitivities of T-ALL cell lines and hMSCs to BCT-100. Apoptosis of T-ALL cell lines with or without BCT-100 treatment were tested by annexin V / propidium iodide (AV/PI) assay using flow cytometer. Western blotting was performed to analyze the expression of ornithine transcarbamylase (OTC), an enzyme involved in L-arginine metabolism which may account for BCT-100 resistance. Results: hMSCs were resistant to BCT-100 while CCRF-CEM, Jurkat and MOLT-4 were very sensitive to it. hMSCs could protect all the three cell lines from BCT-100 treatment in transwell co-culture. All the 3 T-ALL cell lines were also found to be rescued by an L-arginine precursor citrulline, while the breakdown product of BCT-100, ornithine only had limited salvaging effect on CCRF-CEM but not Jurkat and MOLT-4. Both hMSCs and 3 T-ALL cell lines express citrulline synthesis enzyme, ornithine transcarbamylase (OTC) at basal level while only hMSCs could express OTC at relatively higher level under BCT-100 treatment. Treating hMSCs with vincristine before co-culturing with T-ALL could resume the cytotoxicity of BCT-100 to CCRF-CEM and MOLT-4 cells. Conclusions: Our results suggest a possible strategy to overcome resistance to BCT-100 from cancer microenvironments by suppressing hMSCs either in marrow or in the perivascular niche using vincristine. http://www.ehoonline.org/content/2/1/11 Fung Kwong-Lam Chan Chi-Fung Experimental Hematology & Oncology 2013, null:11 2013-04-10T00:00:00Z doi:10.1186/2162-3619-2-11 /content/figures/2162-3619-2-11-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 11 2013-04-10T00:00:00Z XML Background: CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome. Methods: The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples. Results: miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56- vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate. Conclusions: miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis. http://www.ehoonline.org/content/2/1/10 Hamilton Gimenes-Teixeira Antonio Lucena-Araujo Guilherme dos Santos Dalila Zanette Priscila Scheucher Luciana Oliveira Leandro Dalmazzo Wilson Silva-Júnior Roberto Falcão Eduardo Rego Experimental Hematology & Oncology 2013, null:10 2013-04-08T00:00:00Z doi:10.1186/2162-3619-2-10 /content/figures/2162-3619-2-10-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 10 2013-04-08T00:00:00Z XML Less is known about the non-mesenchymal mononuclear cell fraction of human bone marrow on functional adaptation of neuroblastoma cells. Using immunocytochemistry, we showed that bone-marrow mononuclear cell (BMMC)-conditioned medium can induce tyrosine hydroxylase expression in neuroblastoma cells, which is similar to the effect of retinoic acid. Using quantitative RT-PCR, we showed that NGF, CNTF, and BDNF mRNAs were detected in unfractionated BMMC populations from all human donors at different expression levels. Our results suggest that cells of the non-mesenchymal mononuclear cell fraction can induce functional adaptation of neuroblastoma cells, probably via their secreted trophic factors. http://www.ehoonline.org/content/2/1/9 Chareerut Phruksaniyom Permphan Dharmasaroja Surapol Issaragrisil Experimental Hematology & Oncology 2013, null:9 2013-04-03T00:00:00Z doi:10.1186/2162-3619-2-9 /content/figures/2162-3619-2-9-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 9 2013-04-03T00:00:00Z XML Among the dendritic cell (DC) subsets, plasmacytoid DC’s (pDC) are thought to be important in the generation of both antiviral and antitumor responses. While pDC may be useful in developing dendritic cell-based tumor vaccines, the low frequency of these cells in the peripheral blood has hampered attempts to understand their biology. To provide better insight into the biology of pDC, we isolated these unperturbed cells from the peripheral blood of healthy donors in order to further characterize their gene expression. Using gene array technology we compared the genetic profiles of these cells to those of CD14+ monocytes isolated from the same donors and found several immune related genes upregulated in this cell population. This is the first description, to our knowledge, of gene expression in this subset of DCs obtained from the peripheral blood of adult human donors without exposure in vitro to cytokine or growth factors. Understanding the natural genetic profiles of this dendritic cell subtype as well as others such as the BDCA-1 expressing myeloid DCs may enable us to manipulate these cells ex-vivo to generate enhanced DC-based tumor vaccines inducing more robust antitumor responses. http://www.ehoonline.org/content/2/1/8 Stephen Wrzesinski Jan Fisher Marc Ernstoff Experimental Hematology & Oncology 2013, null:8 2013-03-09T00:00:00Z doi:10.1186/2162-3619-2-8 /content/figures/2162-3619-2-8-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 8 2013-03-09T00:00:00Z XML High levels of BAALC, ERG, EVI1 and MN1 expression have been associated with shorter overall survival in AML but standardized and clinically validated assays are lacking. We have therefore developed and optimized an assay for standardized detection of these prognostic genes for patients with intermediate cytogenetic risk AML. In a training set of 147 intermediate cytogenetic risk cases we performed cross validations at 5 percentile steps of expression level and observed a bimodal significance profile for BAALC expression level and unimodal significance profiles for ERG and MN1 levels with no statistically significant cutoff points near the median expression level of BAALC, ERG or MN1. Of the possible cutoff points for expression levels of BAALC, ERG and MN1, just the 30th and 75th percentile of BAALC expression level and the 30th percentile of MN1 expression level cutoff points showed clinical significance. Of these only the 30th percentile of BAALC expression level reproduced in an independent verification (extended training) data set of 242 cytogenetically normal AML cases and successfully validated in an external cohort of 215 intermediate cytogenetic risk AML cases. Finally, we show independent prognostic value for high EVI1 and low BAALC in multivariate analysis with other clinically relevant molecular AML markers. We have developed a highly standardized molecular assay for the independent gene expression markers EVI1 and BAALC. http://www.ehoonline.org/content/2/1/7 Jaap Brand Martin van Vliet Leonie de Best Peter Valk Henk Viëtor Bob Löwenberg Erik van Beers Experimental Hematology & Oncology 2013, null:7 2013-03-06T00:00:00Z doi:10.1186/2162-3619-2-7 /content/figures/2162-3619-2-7-toc.gif Experimental Hematology & Oncology 2162-3619 ${item.volume} 7 2013-03-06T00:00:00Z XML