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Experimental Hematology & Oncology

Magdalena Kovacsovics-Bankowski, Todd W Kelley, Olga Efimova, Soo Jin Kim, Andrew Wilson, Sabina Swierczek, Josef Prchal
BACKGROUND: Pegylated-interferon alpha (PegINFα) treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) has resulted in long-term clinical response, decreased JAK2(V617F) allelic burden and restoration of polyclonal hematopoiesis. The mechanisms of the beneficial effects of PegINFα are not clear, but available evidence suggests direct suppression of JAK2-mutated clone, induction of dormant stem cells to proliferation, and augmentation of an immune effect against PV and ET clones...
2015: Experimental Hematology & Oncology
Joseph M Wu, Ardalan Oraee, Barbara B Doonan, John T Pinto, Tze-Chen Hsieh
BACKGROUND: The NAD(P)H: quinone oxidoreductase (NQO1) confers protection against semiquinones and also elicits oxidative stress. The C609T polymorphism of the NQO1 gene, designated NQO1*2, significantly reduces its enzymatic activity due to rapid degradation of protein. Since down regulation of NQO1 mRNA expression correlates with increased susceptibility for developing different types of cancers, we investigated the link between leukemia and the NQO1*2 genotype by mining a web-based microarray dataset, ONCOMINE...
2015: Experimental Hematology & Oncology
Zihai Li, Delong Liu
No abstract text is available yet for this article.
2015: Experimental Hematology & Oncology
Hanna Grauers Wiktorin, Tina Nilsson, Ann Jansson, Lars Palmqvist, Anna Martner
BACKGROUND: Acute myeloid leukemia (AML) carrying nucleophosmin 1 (NPM1) mutations (NPMc(+)) is regarded as a separate entity of myeloid neoplasms due to its distinct biological and clinical features. However, NPMc(+) alone displays low leukemogenic activity and cooperating events appear crucial for AML to develop. Dysregulation of homeobox genes, such as HOXA9 and MEIS1, is a common transcriptional signature of NPMc(+) AML. Furthermore, the pathogenic role for NPMc(+) in AML remains incompletely understood...
2015: Experimental Hematology & Oncology
David Berz, Victoria M Raymond, Jordan H Garst, Mark G Erlander
BACKGROUND: The increasing understanding of non-small cell lung cancer (NSCLC) biology over the last two decades has led to the identification of multiple molecular targets. This led to the development of multiple targeted therapies in the primary and secondary resistance setting and the epidermal growth factor receptor (EGFR) gene remains the most frequently observed molecular target in NSCLC. Tissue biopsies remain the standard for the identification of such EGFR mutations. Obtaining serial tissue biopsies, especially in the secondary resistance setting is associated with multiple medical and logistical challenges...
2015: Experimental Hematology & Oncology
Eddy C Hsueh, Kalyan C Gorantla
With the rapid succession of new effective agents for melanoma in the recent years, the paradigm for treatment of metastatic melanoma is changing. The success of combining multiple effective agents compared with outcomes of monotherapy also brings increasing complexity in the treatment algorithm for various subsets of metastatic melanoma patients. We reviewed the recent reports on novel melanoma therapy to shed light on rational decision-making in treating these patients.
2015: Experimental Hematology & Oncology
Suleiman Al-Hammadi, Saeeda Almarzooqi, Alia Albawardi, Abdul-Kader Souid
BACKGROUND: Blocking mTOR (molecular target of rapamycin) by sirolimus has been shown to suppress cellular respiration. The bearing of this impaired cellular bioenergetics on the mode-of-action of mTOR inhibitors has yet to be illustrated. METHODS: This study investigated in vitro effects of several molecularly-targeted therapies on O2 consumption in thymic fragments from C57BL/6 mice. RESULTS: Thymocyte respiration (µM O2 min(-1) mg(-1)) was reduced by sirolimus and everolimus (p ≤ 0...
2015: Experimental Hematology & Oncology
Bernardo López-Andrade, Francesca Sartori, Antonio Gutiérrez, Lucia García, Vanesa Cunill, María Antonia Durán, Antonia Sampol, Marta Bernués, Julio Iglesias, Rafael Ramos, Josep Lladó, María Sánchez, Juan Carlos Amat, Jordi Martínez-Serra
B Acute Lymphoblastic leukemia (B-ALL) with Philadelphia chromosome (Ph') is a neoplasm of lymphoblast committed to the B cell lineage. The clinical presentation of B-ALL Ph'+ is similar to B-ALL, but is more common in adults than in children. The e1a3 rare variant is produced by the fusion of BCR exon 1 to ABL exon 3. The presence of this translocation has been associated with good disease outcome for chronic myeloid leukemia in a very small series of only 5 cases; there is no such evidence for B-ALL. We report two new cases of B-ALL Ph+ with the rare e1a3 fusion transcript...
2015: Experimental Hematology & Oncology
Katherine Linder, Deepthi Gandhiraj, Madhura Hanmantgad, Karen Seiter, Delong Liu
BACKGROUND: The current standard of care for relapsed and refractory acute lymphoblastic leukemia (ALL) is combination chemotherapy. CASE PRESENTATION: We report a case of highly refractory ALL who was treated with blinatumomab. The ALL in this patient relapsed within a month after completion of hyperCVAD regimen and was refractory to high dose mitoxantrone/cytarabine and CLAG regimens. CONCLUSION: This highly refractory pre-B Ph(-) ALL was induced to complete remission after one course of single agent blinatumomab...
2015: Experimental Hematology & Oncology
Tao Liu, Xiaobo Li, Shuo You, Soumitra S Bhuyan, Lei Dong
AMD3100, also known as plerixafor, was originally developed as an anti-human immunodeficiency virus (HIV) drug, and later characterized as a C-X-C chemokine receptor type 4 (CXCR4) antagonist. Previous reviews have focused on the application of AMD3100 in the treatment of HIV, but a comprehensive evaluation of AMD3100 in the treatment of leukemia, solid tumor, and diagnosis is lacking. In this review, we broadly describe AMD3100, including the background, functional mechanism and clinical applications. Until the late 1990s, CXCR4 was known as a crucial factor for hematopoietic stem and progenitor cell (HSPC) retention in bone marrow...
2015: Experimental Hematology & Oncology
Lisa Repsold, Etheresia Pretorius, Annie Margaretha Joubert
BACKGROUND: Platelets are known contributors to the vascularization, metastasis and growth of tumors. Upon their interaction with cancer cells they are activated resulting in degranulation and release of constituents. Since the apoptotic- and autophagic effects of 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) has been shown to occur in vitro and this compound was designed to bind to carbonic anhydrase II (CAII), the possible occurrence of these cell death mechanisms in platelets as circulatory components, is of importance...
2015: Experimental Hematology & Oncology
Jingchen Shao, Susann Li, Lars Palmqvist, Linda Fogelstrand, Stella Y Wei, Kiran Busayavalasa, Kui Liu, Viktor M Liu
PTEN acts as a phosphatase for PIP3 and negatively regulates the PI3K/AKT pathway, and p27(KIP1) is a cyclin-dependent kinase inhibitor that regulates the G1 to S-phase transition by binding to and regulating the activity of cyclin-dependent kinases. Genetic alterations of PTEN or CDKN1B (p27(KIP1)) are common in hematological malignancies. To better understand how mutations in these two genes might cooperate in leukemogenesis, we inactivated both genes in the hematological compartment in mice. Here, we show that the combined inactivation of Pten and Cdkn1b results in a more severe myeloproliferative neoplasm phenotype associated with lower hemoglobin, enlarged spleen and liver, and shorter lifespan compared to inactivation of Pten alone...
2015: Experimental Hematology & Oncology
Piers R Boshier, Rosie Sayers, Dimitri J Hadjiminas, Charles Mackworth-Young, Susan Cleator, Daniel R Leff
BACKGROUND: Inflammatory breast cancer is a complex pathological entity associated with poor outcomes. This loco-regional disease is characterised by a rapid clinical course in the presence breast erythema and infiltration of dermal lymphatics by tumours cells. Herein we describe a case of inflammatory breast cancer with a rare presentation and disease course defined by a profound systemic inflammatory response in the absence of an infective cause. CASE PRESENTATION: The patient presented with pyrexia and malaise following a recent tissue diagnosis of inflammatory breast cancer...
2015: Experimental Hematology & Oncology
Thy Pham, Martin C Sadowski, Huika Li, Derek J Richard, Michael C d'Emden, Kerry Richard
Hormonal manipulation plays a significant role in the treatment of advanced hormone naïve prostate cancer and castration-resistant prostate cancer (CRPC) with or without previous chemotherapy. Combination of gonadotropin releasing hormone (GnRH) agonists and androgen receptor (AR) antagonists (combined androgen blockade; CAB) is the first line therapy for advanced hormone naïve prostate cancer, but current strategies are developing novel GnRH antagonists to overcome disadvantages associated with GnRH agonist monotherapy and CAB in the clinical setting...
2015: Experimental Hematology & Oncology
Mary Frances McMullin, Glen James, Andrew S Duncombe, Frank de Vocht, Lin Fritschi, Mike Clarke, Lesley A Anderson
BACKGROUND: Myeloproliferative neoplasms (MPNs) including the classic entities; polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis are rare diseases with unknown aetiology. The MOSAICC study, is an exploratory case-control study in which information was collected through telephone questionnaires and medical records. METHODS: As part of the study, 106 patients with MPN were asked about their perceived diagnosis and replies correlated with their haematologist's diagnosis...
2015: Experimental Hematology & Oncology
Toni K Roberts, Xueyan Chen, Jay Justin Liao
BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a recently recognized B cell lymphoproliferative disorder that is driven by latent EBV infection and causes discrete ulcerations in the oropharynx, gastrointestinal tract, and skin. Local attenuation of immunosurveillance associated with iatrogenic immunosuppressant use, primary immunodeficiency, or age-associated immunosenescence has been implicated as a predisposing factor. This disorder is likely under reported, as it was only first defined in 2010 and shares histological features with other B-cell proliferative neoplasms...
2015: Experimental Hematology & Oncology
Gege Feng, Robert Peter Gale, Wen Cui, Wenyu Cai, Gang Huang, Zefeng Xu, Tiejun Qin, Yue Zhang, Bing Li, Liwei Fang, Hongli Zhang, Lijuan Pan, Naibo Hu, Shiqiang Qu, Jingya Wang, Yajuan Cui, Zhijian Xiao
BACKGROUND: Dys-megakaryopoiesis is defined as ≥10 % of dysplastic megakaryocytes in bone marrow smears by the World Health Organization. However, concordance rates for dysplastic megakaryocytes between different observers is low and, consequently, evaluation of dysmegakaryopoiesis is also often discordant. RESULTS: We performed CD41 immune staining and proposed a systematic classification of dys-megakaryopoiesis on bone marrow films: (1) micro-megakaryocytes (<12 µm); (2) micro-megakaryocytes (12-40 µm) with 1 nucleus; (3) micro-megakaryocytes (12-40 µm) with 2 nuclei; (4) micro-megakaryocytes (12-40 um) with multiple (more than 2) nuclei; (5) dysplastic megakaryocytes (≥40 µm) with 1 nucleus; (6) dysplastic megakaryocytes (≥40 µm) with 2 nuclei; and (7) dysplastic megakaryocytes (≥40 µm) with multiple (more than 2) nuclei...
2015: Experimental Hematology & Oncology
Tatsuo Ichinohe, Yoshiaki Kuroda, Shinichiro Okamoto, Kosei Matsue, Shinsuke Iida, Kazutaka Sunami, Takuya Komeno, Kenshi Suzuki, Kiyoshi Ando, Masafumi Taniwaki, Kensei Tobinai, Takaaki Chou, Hitomi Kaneko, Hiromi Iwasaki, Chie Uemura, Hiromi Tamakoshi, Mohamed H Zaki, Thomas Doerr, Shotaro Hagiwara
BACKGROUND: The immunomodulatory agent pomalidomide in combination with low-dose dexamethasone has demonstrated efficacy and safety for the treatment of relapsed and refractory multiple myeloma (RRMM) in phase 2 and 3 trials. However, these trials enrolled very few Asian patients. METHODS: This phase 2 study investigated pomalidomide plus low-dose dexamethasone in 36 Japanese patients with RRMM after ≥2 prior therapies. RESULTS: Patients enrolled in the study had a relatively high disease burden (81 % Durie-Salmon stage II or III) and were heavily pretreated (median, 6...
2015: Experimental Hematology & Oncology
Clémentine Gamonet, Elodie Bole-Richard, Aurélia Delherme, François Aubin, Eric Toussirot, Francine Garnache-Ottou, Yann Godet, Loïc Ysebaert, Olivier Tournilhac, Caroline Dartigeas, Fabrice Larosa, Eric Deconinck, Philippe Saas, Christophe Borg, Marina Deschamps, Christophe Ferrand
[This corrects the article DOI: 10.1186/s40164-016-0036-3.].
2015: Experimental Hematology & Oncology
Jun S Liu, Sumati Rao
BACKGROUND: For unresectable or metastatic melanoma, first-line ipilimumab has demonstrated long-term survival benefits over a 7-year period. First-line treatment with BRAF inhibitors has demonstrated efficacy in clinical trials with up to 3 years of follow-up. The long-term comparative efficacy and costs of ipilimumab and BRAF inhibitors are unknown. METHODS: Patient-level data from 12 clinical studies for ipilimumab were used. Survival data were extracted from included clinical trials for BRAF inhibitors based on a systematic literature review...
2015: Experimental Hematology & Oncology
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