bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myelodysplasia (MDS) patients' Experiences with Blood Transfusions
Authors: Twiss James , McKenna Stephen P , Crawford Sigrid Rebecca , Wilburn Jeanette N , Loth Kevin , Mufti Ghulam J 
Published: October 2019

Abstract
Abstract 5033

Introduction:
Although the main treatment for MDS is blood transfusions, scarce information is available on patients' experiences of the treatment. Only one relevant study could be identified which reported that patients have a preference for being transfusion independent (Szende et al. Valuation of transfusion-free living in MDS: results of health utility interviews with patients. (2009). Health Qual Life Outcomes, 7:81). As part of a study investigating the effect of MDS and its treatment on quality of life, patients were asked about their experiences with transfusions.

Methods:
Qualitative, unstructured interviews were conducted with MDS patients. Verbatim transcripts were produced and subjected to Interpretative Phenomenological Analysis (IPA). IPA aims at gaining an understanding of patients' experiences from their own perspective. Themes are generated based on issues identified during the interview process.

Results:
The sample included 23 patients with blood transfusion experience (male = 11 (47.8%); mean (SD) Age=65.3 (11.2)). Of the patients interviewed, 9 (39.1%) were currently receiving regular transfusions, 5 (21.7%) had been transfusion dependent previously and 9 (39.1%) had some transfusion experience. Illness information for these interviewees is shown in the Table 1. Five major themes were identified in the analyses; positive aspects of transfusions, the cyclic nature of symptoms, transfusion-related limitations on functioning, associated iron chelation therapy and problems with actually receiving the transfusions. Transfusions were perceived positively by some patients as they relieve patients' everyday symptoms. However, these benefits diminish between transfusions leading to cycles of good and poor symptoms, functioning and psychological distress. Limitations to patients' lives resulted from frequent and often long trips to hospital. Patients reported negative experiences with the iron chelating drug Deferrioxamine which is needed to reduce iron poisoning. The drug is generally administered subcutaneously by means of a battery operated pump and is usually worn for several hours a day causing pain and discomfort. The transfusions were also reported to be boring, uncomfortable and at times painful.

Conclusions:
Transfusions can have a large negative impact on patient's lives. The results suggest there is a need for alternative forms of treatment for patients with MDS. Further quantitative work assessing patients' experiences with transfusions is required.

Disclosures:
Twiss: Celege Ltd: Consultancy, Research Funding. McKenna:Celgene Ltd: Consultancy, Research Funding. Crawford:Celegene: Consultancy, Research Funding. Wilburn:Celegene Ltd: Consultancy, Research Funding. Loth:Celgene Ltd: Employment.
Expression of dlk1 in the Bone Marrow Cells of Patients with Myelodysplastic Syndrome and Its Clinical Significance
Authors: Shao Zonghong , Yue Lanzhu , Fu Rong , Li Lijuan , Ruan Erbao , Qu Wen , Liang Yong , Wang Guojin , Wang Xiaoming , Liu Hong , Song Jia , Wu Yuhong , Xing Limin , Wang Jun , Guan Jing , Wang Huaquan 
Published: October 2019

Abstract
Abstract 5042

Objective
To investigate the expression of dlk1 gene (delta-like 1) in the bone marrow cells of patients with Myelodysplastic syndrome (MDS), and explore the molecular marker for early diagnosis of MDS.

Methods
The expression of dlk1 mRNA in the bone marrow cells of cases with MDS, AML and normal controls were measured by RT-PCR, aiming to search for the cytogenetic marker of MDS malignant clone.

Results
The expression of dlk1 mRNA in bone marrow cells of MDS patients (0.7342±0.3652) was significantly higher than that of normal controls (0.4801±0.1759) (P<0.05), and was significantly positively correlated with the proportion of bone marrow blasts(r=0.467,P<0.05). The expression of dlk1 mRNA significantly increased as the subtype of MDS advanced (P<0.05). Patients with abnormal karyotypes displayed significantly higher expression of dlk1 mRNA (0.9007±0.4334) than those with normal karyotypes (0.6411±0.2630) (P<0.05). Patients with higher expression of dlk1(≥0.8) presented significantly higher malignant clone burden (0.4134±0.3999) than those with lower expression (<0.8) of dlk1 (0.1517±0.3109) (P<0.05).

Conclusion
dlk1 gene was highly expressed in MDS patients, which increased as the subtype of MDS advanced. The expression of dlk1 mRNA was significantly positively correlated with the proportion of bone marrow blasts. High expression of dlk1 gene suggests high malignant clone burden of MDS.

Disclosures:
No relevant conflicts of interest to declare.
Methylation Analysis of the Wnt Antagonist in Myelodysplastic Syndrome
Authors: Tong Hongyan , Mei Chen , Li Kongfei , Jin Jie 
Published: October 2019

Abstract
Abstract 5048

Background and Objectives:
Myelodysplastic syndrome (MDS) is one of the most threatening hematological malignancies. Recently, the epigenetic changes have been recognized in the MDS, and some research found that the aberrant DNA methylation had close relationship with the MDS. Meanwhile, some studies showed that the activation of the Wnt signaling pathway and abnormal methylation of the Wnt antagonists had close relationship with hematological malignancies, such as AML AALL Aand CLL, but less is known in MDS. In our research, we studied the methylation status of Wnt antagonists (DKK1, DKK3, HDPR1, WIF-1, SFRP1 and SFRP4) in the patients with MDS and evaluated the role of them in the pathogenesis and progression of MDS, with providing a new theory support for clarifying the complicated pathogenesis and progression of MDS.

Methods:
The methylation status of Wnt antagonists (DKK1, DKK3, HDPR1, WIF-1, SFRP1 and SFRP4) in pretreatment bone marrow samples from 53 patients with MDS was measured by methylation-specific polymerase chain reaction (MSP). On the other hand, we collected the clinical materials of the patients with MDS and follow up the patients. Then the correlation between methylation and clinical features as well as prognosis of MDS patients was analyzed byχ2 test and Kaplan-Meier method. Results: In 53 bone marrow samples, the methylation frequencies of the Wnt antagonists were as follows: SFRP4 for 62.3 % (33/53), DKK1 for 45.3 % (24/53), HDPR1 for 34.0 % (18/53), SFRP1 for 15.1 % (8/53), DKK3 for 9.4 % (5/53), and WIF-1 for 5.7 % (3/53). After analyzing individual tumor suppressor gene, clinical parameters and prognostic information, it was found that the patients with the percentage of BM blast above 5% had higher methylation frequency of HDPR1 than the patients with the percentage of BM blast bellow 5% (44.4%∼a13.3%, P=0.034); besides, the methylation frequency of HDPR1 exhibited significant differences in the MDS subtypes (P=0.019), and was significantly correlated with the WPSS (P=0.037); In addition, Kaplan-Meier survival curve indicated that the mean overall survival of patients with methylation was significantly shorter than that of patients without HDPR1 methylation (457.3 days vs. 919.6 days, P=0.037) (Fig.1).

Conclusion:
The methylation of the Wnt antagonists (DKK1, DKK3, HDPR1, WIF-1, SFRP1 and SFRP4) were observed in patients with MDS and their methylation frequencies were different. The aberrant methylation of HDPR1 may play an important role in the progression and prognosis of MDS.

Disclosures:
No relevant conflicts of interest to declare.
Multiple Myeloma with Secretory and Non-Secretory Biclonal Gammopathy
Authors: Vinayek Namita , Kloecker Goetz H , Riley Beth C. 
Published: October 2019

Abstract
Abstract 5092
Multiple myeloma (MM) accounts for 10 % of hematological malignancies. MM with biclonal gammopathy are rare and seen in 1 % of all MM cases. In 99% of the MM cases, paraproteins are secreted in the serum and/or urine, in the remaining 1% the paraproteins are synthesized but not secreted. Only 2 % of patients are younger than 40 years of age.
We report a 36 year old African American female who presented with diffuse lytic lesions. Serum electrophoresis (SPEP) revealed IgG kappa M protein of 3.8 g/dl and a IgG Kappa M spike of 2.6 mg/dl. Free light chains (SFLC) revealed elevated free kappa chains of 500 mg/dl, elevated free lambda chains of 928 mg/dl and K/L ratio of 0.55. Urine protein UPEP showed an M spike of IgG kappa and free kappa light chains. The B2 microglobulin was 26.8 mg/dl. Patient's recent T10 Bone biopsy done at outside hospital had a near complete replacement of the marrow by plasma cells which were biclonal plasma cells by IHC, one kappa restricted and one lambda restricted. Since the IFE showed only a single IgG kappa M protein spike, the lambda plasma clone was apparently non-secretory.
Treatment was started with cyclophosphamide, bortezomib and dexamethasone. After 22 days of treatment, the M protein has decreased 1.39 mg/dl. A repeat SFLC also shows further decline in free kappa light chains. As the IFE showed one gamma M spike and bone biopsy had two clonal plasma cells it was concluded that one of the neoplasms is nonsecretory. Although the elevated lambda free light chain in the serum is now does point towards a second plasma cell neoplasm.
Biclonal gammopathy is rare and accounts for 1% of all MM cases. To our knowledge, this is the first reported case of a biclonal, secretory and nonsecretory, gammopathy

Disclosures:
No relevant conflicts of interest to declare.
The Nestin Expression in Monoclonal Gammopathies
Authors: Kovarova Lucie , Svachova Hana , Muthu Raja Karthick Raja , Varmuzova Tamara , Zarbochova Pavla , Penka Miroslav , Hajek Roman 
Published: October 2019

Abstract
Abstract 5111

Background.
Monoclonal gammopathies (MG) are the most common plasma cell disorders characteristic by a presence of clonal plasma cells (PCs). The nestin is considered to be a marker of multipotent proliferative precursors, but recently its expression was found in PCs of multiple myeloma (MM) as well. Consequences of the nestin expression still remain unclear.

Aim.
Phenotypic analysis of the nestin expression in the most frequent MGs and its correlation with other markers.

Patients and Methods.
Total of 45 samples was analyzed [31 newly diagnosed untreated MM patients, 14 untreated monoclonal gammopathy of undetermined significance (MGUS) subjects and 5 non-MG samples]. Whole bone marrow CD38+CD138+ PCs were studied for intracellular expression of nestin and surface expression of CD19, CD20, CD27, CD28, CD33, CD56, and CD117 by flow cytometry.

Results.
Flow cytometric analysis shown the nestin expression in 21.4 % (3/14) of MGUS and 45.2 % (14/31) of MM patients, on the other hand no expression of nestin was found in non-MG controls. Expression of the nestin was relatively homogeneous, but not highly intensive. The nestin positive PCs did not express CD19 and/or CD20, but expression of CD27 was found in 29.4 % (5/17) cases, CD28 in 11.8 % (2/17), CD33 in 5.9 % (1/17), CD44 in 35.3 % (6/17), CD56 in 88.2 % (15/17), and CD117 in 29.4 % (5/17) cases. Statistical analysis did not found any significant correlation and/or difference in phenotype when compared the nestin positive and negative samples, although the nestin negative samples expressed CD56 less frequently then the nestin positive samples [46.4 % (13/28) vs. 88.2 % (15/17)], respectively.

Summary/Conclusion.
Our result showed difference in the nestin expression when compared bone marrow of MGUS subjects with MM patients. Although there was no correlation between the nestin positivity and phenotype of PCs, we suppose that the nestin could associate with unfavorable prognosis but further studies are needed to elucidate its clinical implication in MGs.

Disclosures:
No relevant conflicts of interest to declare.
A Novel Small Molecule with Epigenetic Activity Prolongs Survival in a Mouse Model of Multiple Myeloma Refractory to Standard Drugs
Authors: Vatolin Sergei , Shahper Khan Nazeer , Parker Yvonne , Lindner Daniel , Reu Frederic J. 
Published: October 2019

Abstract
Abstract 5121
Multiple myeloma refractory to bortezomib, IMiDs™, and conventional therapies represents an unmet medical need. An increasing number of patients progress to this stage since treatment related mortality has decreased. To test promising compounds for activity in this setting we established an NSG mouse xenograft model with serial transplantation by tail vein injection of myeloma cells from a patient with IgG kappa myeloma relapsed and refractory to all standard drugs. Eight days after tail vein injection monoclonal human IgG can be detected in serum. Bone marrow engraftment in young (6–12 weeks) NSG mice after sublethal radiation (275cGy) is close to 100% (n=32). Untreated mice die within less than 2 months, usually with liver and spleen metastasis (anti-human CD138 flow cytometry). In a drug screen that used a novel method developed in our lab, chromatin condensation PCR, we identified a non nucleoside compound (4I3) that potently (1mM) reactivated expression of epigenetically silenced genes and displayed cancer-specific growth and survival inhibition in myeloma cell lines but not normal cells. Normal bone marrow cells continued to divide at doses 10x higher than required to kill 80% of myeloma cells. 4I3 suppressed DNMT1 protein but rapid cell kill (within 1–2 days) suggested additional mechanisms which we currently investigate. Given IV to mice after documentation of engraftment by IgG serum immunoblots, it prolonged survival in an ongoing experiment. Updated results will be presented at the meeting.

Disclosures:
No relevant conflicts of interest to declare.
JAK2 Mutation Analysis and Function of Bone Marrow Mesenchymal Stem Cells in Myeloproliferative Neoplasms
Authors: Tian Hong , Xu Yang , Chen Guanghua , Qiao Man , Depei Wu 
Published: October 2019

Abstract
Abstract 5179

Background:
JAK2V617F and JAK2 exon12 mutations in haematopoietic cells were partially responsible for the pathogenesis of myeloproliferative neoplasms (MPN).But it was still unclear whether bone marrow mesenchymal stem cells (BMSCs), the significant component of hemopoiesis microenvironment, were participated in the pathogenesis of MPN.

Objective:
To study the physiopathology characteristics and analyze JAK2 mutation in BMSCs from MPN patients.

Methods:
By searched for the JAK2V617F mutation and exon 12 mutation in 135 MPN patients' blood /bone marrow samples, 20 patients with JAK2V617F mutation, 10 patients with JAK2 exon 12 mutation, 5 JAK2-mutation-negetive patients and 10 healthy donors were recruited. The phenotype, mesenchymal differentiation capacity, expression of hematopoietic and immune molecules and JAK2 mutation of isolated bone marrow BMSCs were detected.

Results:
BMSCs derived from the four groups were found to be similar in morphology, differentiation ability and expression of hematopoietic and immune molecules. Primary study indicated that the isolated BMSCs from patients groups were not able to harbor JAK2 mutation in spite of positive or negative JAK2 mutation in blood /bone marrow samples.

Conclusion:
BMSCs from MPN patients had similar biological characteristics to healthy donors, and BMSCs were not likely involved in pathogenesis of MPN.

Disclosures:
No relevant conflicts of interest to declare.
Selective Disruption of PU.1 in Mature Dendritic Cells Affects Their Tissue Distribution and T Cell Homeostasis
Authors: Iino Tadafumi , Iwasaki Hiromi , Kohno Kentaro , Mizuno Shin-ichi , Arinobu Yojiro , Tenen Daniel G. , Reizis Boris , Akashi Koichi 
Published: October 2019

Abstract
Abstract 518
PU.1, a hematopoietic transcription factor, is indispensable for development of conventional dendritic cells (cDCs) from hematopoietic stem cells. However, the function of PU.1 in mature cDC remains unclear. To test the possible role of PU.1 in mature cDCs, we developed mice lacking PU.1 selectively in mature cDCs (DC-PU.1D/D mice) by crossing a PU.1flox mouse line with a transgenic Itgax (CD11c)-Cre strain. In these mice, cDCs were dramatically reduced in spleen, thymus, lymph node, and skin, down to <40%, <25%, <10% and <5% of DCs in control mice respectively, whereas bone marrow cDCs and common dendritic cells progenitors (CDPs) were not affected. Surprisingly, T cell numbers were significantly decreased in DC-PU.1D/D mice, whereas thymic T cell development was normal, suggesting that maintenance of mature T cell pool might be impaired, presumably by dysfunction of PU.1D/D cDCs. In fact, PU.1D/D cDCs failed to efficiently induce ovalbumin-specific T cell response and to produce inflammatory cytokines in response to Toll like receptor (TLR) stimulation both in vitro and in vivo. The intravenous transfer of spleen PU.1D/D cDCs failed to repopulate the spleen of recipient mice, suggesting their poor survival in vivo. Furthermore, the expression of critical molecules for inflammatory responses was downregulated in PU.1D/D cDCs as compared to normal cDCs. These molecules included Myd88 and NFkB that are downstream molecules of TLR signaling, CD86 that is required for T cell stimulation, and CCR7 that is required for cDC migration. These results clearly show that PU.1 is required for development of the functional cDC pool, and the cDC pool plays a critical role in T cell homeostasis.

Disclosures:
No relevant conflicts of interest to declare.
Characterizing Canine Lymphoma As a Potential Large Animal Model of Human Diffuse Large B-Cell Lymphoma
Authors: Richards Kristy L. , Motsinger-Reif Alison , Chen Hsiao-Wei , Fedoriw Yuri D. , Fan Cheng , Nielsen Dahlia M. , Thomas Rachael , Smith Chris , Dave Sandeep S. , Perou Charles M. , Breen Matthew , Suter Steven E. 
Published: October 2019

Abstract
Abstract 5193
Diffuse large B-cell lymphoma (DLBCL) affects ∼25,000 people in the U.S. each year, and fewer than half of them are cured with standard therapy. DLBCL can be divided into two subtypes by gene expression profiling, germinal center B-cell (GCB) type and activated B-cell (ABC) type. ABC-type DLBCL patients have significantly poorer outcomes. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL is one of the most common cancers in veterinary oncology. Similar to human DLBCL patients, dogs with lymphoma are treated with both CHOP-like regimens and autologous stem cell transplants. Morphologically, canine lymphomas are similar to hDLBCL, with shared histologic markers, such as CD20 and PAX5. With recent technologies based on knowledge of the canine genome sequence, it is now possible to evaluate dogs as a potential large-animal model for hDLBCL.
We evaluated 58 canine B-cell lymphomas by generating comprehensive gene expression profiles and comparing them to previously published hDLBCL expression profiles. Canine B-cell lymphoma expression profiles were similar in some ways to hDLBCLs. For instance, increased expression of NF-kB pathway genes was noted in a subset of lymphomas, mirroring NF-kB pathway activation in human ABC-type DLBCL. Furthermore, immunoglobulin heavy chain (IGH) mutation status, which is correlated with ABC/GCB cell of origin in hDLBCL, separated canine DLBCL into two groups with statistically different progression-free and overall survival times. However, canine DLBCL differed from hDLBCL in other aspects, including rare immunohistochemical positivity for BCL6 and MUM1/IRF4. Collectively, these results define aspects of canine B-cell lymphomas that resemble hDLBCL, identifying molecular similarities that could allow dogs to be used as a representative model of hDLBCL. Further comparative studies, including therapeutic trials, could potentially improve outcomes in both species.

Disclosures:
No relevant conflicts of interest to declare.
Stromal Interaction of Lymphoma Cells Regulates Survival and Chemoresistance
Authors: Park Gyeongsin , Song Byunghoo , Lee Yuji , Lee Ahwon , Chung Yang-Guk , Kang Chang Suk , Oh Il-Hoan 
Published: October 2019

Abstract
Abstract 5195
High-grade lymphomas are aggressive but largely curable, whereas low-grade lymphomas are indolent, but frequently recur to be incurable, paradoxically. Mesenchymal stromal cells (MSCs) have been known to participate for reconstituting microenvironment. Studies show that signalings between normal lymphoid cells and stromal cells were frequently altered in high grade lymphomas, but relatively conserved in low grade lymphomas. However, which cell and mechanism is responsible for lymphoma recurrence remains unclear. Here we hypothesized that the interaction with stroma may play a role for lymphoma cell growth and survival. For this, we investigated the effect of MSCs on lymphoma cell growth and chemo-resistance by using a coculture system with MSCs (derived from tonsil), as a stromal microenvironment for lymphoma cells. First, coculture of lymphoma cell line (Pfeiffer) and primary lymphoma cells with/without MSCs for 3 days showed that the MSC-cocultured cells grew more rapidly (1.4 times and 1.8 times for Pfeiffer and primary cells, respectively) than MSC-free lymphoma cells. To further investigate the underlying mechanism of promoting growth, lymphoma cells were cocultured with MSCs in the presence or absence of transwell filter. At day 4, the proliferation of lymphoma cells in the absence of transwell was 3.5 times higher than in the presence of transwell. Interestingly, the lymphoma cells cocultured with MSCs showed increased expression of CXCR4 compared with lymphoma cells cultured alone. When the cyto-protective effect of MSCs was examined by doxorubicin treatment (1ug/ml) in the presence or absence of MSCs, 91% of MSC-cocultured cells survived, whereas only 28% of stroma-free cultured cells survived. These results demonstrate that the direct contact interaction with stroma might be important for lymphoma cell growth and survival.
In conclusion, our data suggest that the interaction with stromal microenvironment is an important factor for survival of lymphoma cells which cells might be responsible for chemoresistance, and raise the possibility that the stromal interaction could be a potential target for lymphoma treatment.

Disclosures:
No relevant conflicts of interest to declare.
This research was supported by a grant (10172KFDA993) from Korea Food & Drug Administration in 2011.

Disclosures:
No relevant conflicts of interest to declare.