bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Reprogramming of Mesenchymal Stem Cells upon Co-Cultivation with Primary CLL Cells Determined By Mass Spectrometry-Based Proteomics
Authors: Schwarzmeier Josef D. , Mayer Rupert L , Slany Astrid , Bilek Andrea , Christopher Gerner 
Published: October 2019

Abstract
Chronic lyhocytic leukemia displays a strong dependency on tumor-stroma interactions. CLL cells were found to rapidly die when cultivated in vitro, whereas co-cultivation with mesenchymal stromal cells promotes cell proliferation and ensures leukemia cell survival. It is therefore of great interest to obtain a thourough picture of the exact molecular players involved in this critical interplay. While a number of protagonists are already well described, there are still unresoved issues concerning the effect of stromal cells on the metabolism of CLL cells.
In this study we co-cultivated for one week primary CLL cells obtained from peripheral blood with mesenchymal cells (hMSC). Subsequently, hMSC were lysed and fractionated to obtain cytoplamic, nuclear and secreted proteins. To allow comparative analyses, B-cells from healthy individuals and hMSC were co-cultivated.
Mass spectrometry-based proteomic analysis resulted in the identification and relative quantification of more than 3700 proteins. Comparative analyses between co-cultures with CLL and healthy B-cells showed that already at a ratio of 0.25% CLL cells could induce a significant proteomic alteration in hMSC. Furthermore, hMSC were found to undergo a metabolic change upon co-cultivation with CLL cells, an effect which was most pronounced in the secreted protein fraction. Annotation analyses according to gene ontology revealed that proteins related to "generation of precursor metaboites" were significantly up-regulated in hMSC upon co-culture with CLL cells. This indicated that these stromal cells "feed" the leukemia cells by producing and secreting high energy metabolite, satisfying the elevated metabolic demands of the CLL cells.
Revealing the metabolic interactions between CLL cells and surrounding stromal cells by mass spetrometry-based methods should contribute to the development of innovative treatment strategies.

Disclosures
No relevant conflicts of interest to declare.
Does Hypogammaglobulinemia at Diagosis Effects Survival and Infection Risk in Chronic Lymphocytic Leukemia (CLL)?
Authors: Atilla Erden , Ataca Atilla Pinar , Civriz Bozdag Sinem , Toprak Selami Kocak , Topcuoglu Pervin , Ilhan Osman , Ozcan Muhit , Arslan Onder 
Published: October 2019

Abstract
Background: CLL is the most common leukemia in Western World. Hypogammaglobulinemia is the most common immune deficiency detected in CLL. Patients with CLL have increased risk of recurrent infections. Despite hypogammaglobulinemia reported as a cause of both infections and morbidity, controversy exists in its role.
Aim: In the present study, we have evaluated the impact of hypogammaglobulinemia at diagnosis on survival and infection risk in CLL.
Patients and Mathods: We have included 75 CLL patients diagnosed between 2000 and 2014 with B lymphocyte count >5000mm3, CD5, CD19, CD30, CD 23, CD79b positivity and surface Ig light chain restriction in flow cytometry at Ankara University School of Medicine Department of Hematology. The diagnosis and treatment criterias were depended on IWCLL 2008. The patient's performance status was evaluated by physician. If levels were considered decreased when values were below the normal ranges, defined as IgG 6.1-14.9 g/L, IgA 0.8-4.9 g/L and IgM 0.41-2.2 g/L. Overall survival (OS) was calculated by Kaplan-Meier method.
Results: The median age at diagnosis was 59 (range, 32-85). 47 patients (63%) were male. The frequencies of RAI staging from 0 to 4 were as follows; 17%, 13%, 25%, 13%, 32%. The ECOG performance status at diagnosis were stage 1 in 81%, stage 2 in %16, stage 3 in %3 of patients. FISH abnormality was detected in 19 patients (25%), del 13q was the most common. 39 patients (52%) (25 fit, 12 unfit, 2 unknown) received treatment. Fit patients got Rituximab-Fludarabine-Cyclophosphomide (R-FC) in first line whereas RFClite was preferred in unfit patients. 37 patients (49%) had any hypogammaglobulinemia at diagnosis; low IgG in 7 (9%), low IgM in 28 (37%), low IgA in 18 (24%) patients. During first year after diagnosis 26 patients (35%) had moderate to severe infections. Twenty five patients (68%) received intravenous immunoglobulin (IVIG) after diagnosis of hypogamaglobulinemia. No significant associations were found with Ig levels and infections. Six patients died during follow-up. 5-year OS in patients with normal and decreased gammaglobulin were 90% vs 86% (P=0.72). There were no survival advantage detected in low IgG, IgM, IgA subgroup analysis.
Conclusion: Hypogammaglobulinemia is considered predictive risk of infections. However we have not detected any significant increase of infections or decrease of survival in our cohort. Most of patients with hypogammaglobulinemia received IVIG after diagnosis which would effect our results.

Disclosures
No relevant conflicts of interest to declare.
Consolidation Chemotherapy Is Not Beneficial for Adult Acute Lymphoblastic Leukemia Patients with Available Donor Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation in First Complete Remission: A CIBMTR Study
Authors: Bejanyan Nelli , Lazaryan Aleksandr , Zhang Mei-Jie , Wang Hai-Lin , de Lima Marcos , Sandmaier Brenda M. , Horowitz Mary M. , Khoury H. Jean , Weisdorf Daniel J. 
Published: October 2019

Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is potentially curative for patients with ALL who achieve complete remission with upfront chemotherapy (CR1). However, the necessity of consolidation chemotherapy remains uncertain in patients with an available donor undergoing alloHCT, even if the goal is to reduce the detectable disease burden prior to alloHCT. We therefore compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 cycles (n=109) vs. 1 cycle (n=93) vs. no (n=322) consolidation chemotherapy prior to myeloabalative alloHCT from 2008-2012. The median follow up of survivors was 59 (6-78) months. All three consolidation groups had similar patient, disease and transplant characteristics, but no consolidation patients were older, took longer to achieve CR1 and less frequently received CNS prophylaxis or maintenance chemotherapy prior to alloHCT. In contrast, fewer with 1 cycle consolidation had prior comorbidities. Time to alloHCT was longer with increasing cycles of consolidation. Only a minority had either cytogenetic or molecular detectable disease in their pre-HCT CR1 assessment; and it was similar in each consolidation cohort. For ≥2 cycles, 1-cycle, no consolidation groups, the adjusted 3-year cumulative incidence of relapse was 20%, 27% and 22% and 1-year transplant-related mortality (TRM) was 16%, 18% and 23%, respectively (all p-values > 0.4). Similarly, adjusted 3-year leukemia-free survival (LFS) was 54%, 48% and 47% (Figure), while overall survival (OS) was 63%, 59% and 54%, respectively (all p-values > 0.3). Consolidation did not influence acute or chronic GVHD risks. Multivariable regression analysis adjusted for recipient age, Karnofsky performance status, time to CR1, graft source, donor type and recipient CMV serostatus, confirmed that consolidation chemotherapy was not prognostic of LFS (RR=1.20, 95% CI 0.86-1.67; p=0.28 for no consolidation; RR=1.18, 95% CI 0.79-1.76; p=0.41 for 1 cycle; ≥2 cycles=reference). Similarly, consolidation was not associated with OS, relapse, TRM or GVHD. We conclude that consolidation chemotherapy does not benefit adult ALL patients with readily available donor who undergo myeloablative alloHCT in CR1.
Figure. Figure.

Disclosures
No relevant conflicts of interest to declare.
A Runx1 Interactome Identifies Novel Hematopoietic Enhancers
Authors: Marsman Judith , Thomas Amarni L , Osato Motomi , O'Sullivan Justin M , Horsfield Julia A 
Published: October 2019

Abstract
The transcription factor Runx1 is essential for definitive hematopoiesis, and human RUNX1 is frequently translocated or mutated in leukaemia. Runx1 expression from its two promoters, the proximal P1 and distal P2, must be tightly regulated for normal hematopoiesis to occur. The mechanism(s) of promoter-specific Runx1 expression during development and differentiation of hematopoietic progenitors is poorly understood. Gene regulatory elements located in non-coding DNA, such as the previously identified +24 enhancer (Ng et al, Stem Cells 2010), are likely to be important for Runx1 transcription. Here, we identify novel cis-regulatory DNA elements that are competent to drive hematopoietic expression in zebrafish, and that interact long-range with the Runx1 gene.
Circular chromosome conformation capture sequencing (4C-seq) was used to identify long-range interactions of DNA elements with the promoters of Runx1 in the mouse hematopoietic progenitor cell line, HPC7. We used the P1 and P2 promoters and the +24 enhancer (located 24 kb downstream from the P1 promoter) as anchor points from which to view cis-interactions on mouse chromosome 16. 4C-seq reveals that high levels of chromatin interactions at Runx1 are contained within a 1 megabase domain, spanning from the upstream Setd4 gene to the downstream Clic6 gene. A comparison with HiC data in K562 cells shows that the same domain is conserved in humans.
HPC7 cells express Runx1 almost exclusively from the P1 promoter, such that DNA elements interacting with P1 are likely to activate gene expression. The active P1 promoter interacts with multiple non-coding regions both upstream and downstream of Runx1-P1. Interacting regions were overlapped with DNAse hypersensitivity peaks and transcription factor binding sites (available in the USCS genome browser) to identify putative enhancers for Runx1. The majority of putative enhancer regions function as blood specific enhancers in zebrafish (Table). Interestingly, the previously identified +24 enhancer interacted promiscuously within and outside of the 1 megabase Runx1 domain, indicating it may regulate the expression of many additional genes. Overall, our study of the Runx1 interactome identifies multiple novel hematopoietic enhancers that directly interact with the P1 promoter of Runx1, suggesting they are likely involved in regulating Runx1 expression.
Table Table.

Disclosures
No relevant conflicts of interest to declare.
Influence of Lower Dose Antithymocyteglobulin As Conditioning Regimen on Viral Infection after Haploidentical Allogeneic Stem Cell Transplantation
Authors: Lin Ren , Wang Yu , Huang Fen , Fan Zhiping , Zhang Shen , Yang Ting , Xu Yajing , Liang Xinquan , Ji Yu , Xu Na , Xuan Li , Ye Jieyu , Sun Jing , Huang Xiaojun , Liu Qifa 
Published: October 2019

Abstract

Background: Antithymocyteglobulin (ATG), used as conditioning regimen, can reduce graft-versus-host disease (GVHD) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Notwithstanding, immunosuppressive effect of ATG may increase the risk of viral infections after HSCT. To evaluate the effect of different doses of ATG on post-transplant viral infection, we conducted a multicenter prospective study to compare EBV and CMV infection in haplo-HSCT recipients receiving 7.5 mg/kg or 10 mg/kg ATG.
Methods
Between May 2013 and November 2015, 350 consecutive patients with hematological malignancies undergoing haplo-HSCT were randomized in 5 hospitals. One hundred and seventy-two patients received ATG with a total dosage of 7.5 mg/kg and 175 received 10 mg/kg ATG. Three patients did not received allocated intervention and transplantation due to leukemia relapse before transplant or toxicity of conditioning regimens.
Results
The cumulative incidence of EBV viremia on day 180 was 23.3±3.2% in 7.5 mg/kg ATG arm which was lower than that in 10 mg/kg arm (34.6±3.7%, P=0.037). CMV viremia were comparable in the two arms (7.5 mg/kg arm: 79.0±3.1% vs. 10 mg/kg arm: 76.9±3.2%, P=0.950). The incidences of CMV diseases were 0.6±0.6% and 2.4±1.2% in 7.5 mg/kg and 10 mg/kg arms, respectively (P=0.093). No difference in the incidence of post-transplant lymphoproliferative disorder (PTLD) was found between the two arms (2.4±1.2% in 7.5 mg/kg arm vs. 5.4±1.8% in 10 mg/kg arm, P=0.150). Besides, acute GVHD grade II to IV within 100 days occurred in 55 recipients with the incidence of 31.4% in 7.5mg/kg ATG arms and 45 recipients in 10 mg/kg arms with the incidence of 26.2% (P=0.279). The incidences of aGVHD grade III to IV were similar in the two arms (8.0% in 7.5 mg/kg arm: vs. 4.7% in 10 mg/kg arm, P=0.196). The 2-years overall survival were 69.5±4.7% and 69.4±3.9% for 7.5 mg/kg and 10 mg/kg group (P=0.540).
Conclusion
Compared with 10 mg/kg of ATG, the application of 7.5 mg/kg might reduce the risk of EBV infection after haplo-HSCT and not increase aGVHD.

Disclosures
Lin: National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding; National Natural Science Foundation of China 81400141: Research Funding.
Treatment of Myeloma Cast Nephropathy (MCN): A Randomized Trial Comparing Intensive Haemodialysis (HD) with High Cut-Off (HCO) or Standard High-Flux Dialyzer in Patients Receiving a Bortezomib-Based Regimen (the MYRE Study, by the Intergroupe Francophone du Myélome (IFM) and the French Society of Nephrology (SFNDT))
Authors: Bridoux Frank , Pegourie Brigitte , Augeul-Meunier Karine , Royer Bruno , Joly Bertrand , Lamy Thierry , Kolb Brigitte , Benboubker Lofti , Arnulf Bertrand , Jaccard Arnaud , Chevret Sylvie , Fermand Jean-Paul 
Published: October 2019

Abstract

Multiple myeloma (MM) is often revealed by acute kidney injury (AKI) usually related to MCN. Recovery of renal function is a key prognostic factor. With novel anti-myeloma agents, HD-independence occurs in about 30% of pts with severe AKI, advocating for the use of additional strategies to rapidly remove circulating monoclonal free light chains (FLC).
We designed a prospective randomized trial to compare the HD-independence rate in pts with inaugural severe AKI secondary to biopsy-proven MCN, treated by intensive HD (8 sessions over the first 10 days, then thrice a week) using either a HCO dialyzer or a conventional high-flux dialyzer. In both groups, pts received 21-day courses of Bortezomib and dexamethasone (BD), reinforced by cyclophosphamide after 3 cycles in the absence of haematological response (HR).
Between 2011 and 2015, 98 pts were randomised. One pt withdrew consent, and 3 had main exclusion criteria. Baseline characteristics in the control arm (n=48) and HCO arm (n=46) were close, including similarly high serum FLC levels (median 6,015mg/L).
HD independence was achieved in 33% and 43% (p= 0.31) at 3 and in 37.5% and 60 % (p=0.03) at 6 mo, in the control and HCO arms, respectively. HR rate of very good partial response or above at 3 mo based on FLC was 48% in control and 59% in HCO groups (p=0.29). Tolerance of HD schedule and of chemotherapy was acceptable in both arms. At 12 mo, 17 pts have died (10 vs 7).
This randomized trial demonstrates that in MM patients with MCN and severe AKI treated with a bortezomib-based regimen, intensive HCO-HD results in higher renal recovery rate than HD with conventional high-flux dialyzers.

Disclosures
Augeul-Meunier: janssen: Consultancy; gilead: Consultancy. Benboubker:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.
An Improved Method for Isolating Viable Human Leukocytes from Peripheral Blood
Authors: LAPIN JOSEPH H. , HORONICK ANDREW , LAPIN ROBERT H. 
Published: October 2019

Abstract
In an effort to isolate human leukocytes as free as possible of erythrocytes, a two-stage method has been studied. The initial step, sedimentation of the erythrocytes with Dextran results in a diminution of RBC:WBC ratio from the 1000:1 of peripheral blood, to 2.34:1. After sedimentation in isotonic saline, the RBC:WBC ratio is decreased to 0.16:1.
This method should prove valuable in preparing leukocytes for immunologic studies.
Chediak’s Anomaly of Leukocytes in Malignant Lymphoma Associated with Leukemic Manifestations: Case Report with Necropsy
Authors: EFRATI P. , JONAS W. 
Published: October 2019

Abstract
A case of Chediak’s anomaly of leukocytes was described, the fourth reported in the literature.
The patient was an 11-month-old boy who, in addition to Chediak’s anomaly of the leukocytes, presented a leukemic blood picture.
He died five days after admission to the hospital, and necropsy revealed a malignant lymphoma.
We consider it possible that in all the reported cases there were generalized pathologic changes in the reticulohistiocytic system.
An Electronic Blood-Cell-Counting Machine
Authors: CROSLAND-TAYLOR P. , STEWART J. W. , HAGGIS G. 
Published: October 2019

Abstract
An electronic blood cell counting machine operating on a flow principle is described. It is quick and easy to use; it can perform a red cell count in ten seconds with an accuracy of ± 2.1 per cent (that is, 5000 cells counted in 10 seconds for a 5 M count). Leukocyte counts can also be performed in ten seconds with an accuracy of ± 9 per cent for a single count (500 cells counted in a 5000 cu.cm. count).
Starch Block Electrophoretic Studies of Human Hemoglobin Solutions I. Technic and Results in the Normal Adult
Authors: MASRI M. S. , JOSEPHSON AARON M. , SINGER KARL 
Published: October 2019

Abstract
1. Erythrocyte hemolysates from hematologically normal, adult individuals were studied by means of starch block electrophoresis.
2. The electrophoretic patterns obtained indicated the presence, in addition to the main component of A hemoglobin A1, of three other hemoglobin fractions designated as A2, A3 and A4, A2 and A4 move slower, while A3 moves faster in alkaline buffer. These components were isolated by elution from the starch after separation by electrophoresis.
3. The concentrations of the various fractions in the hemolysates were estimated from a sample of normal individuals investigated.
4. In our experiments, electrophoretic patterns obtained on starch that has been re-used as a supportive medium for electrophoresis were somewhat different but comparable to those obtained on starch that was used for the first time as a supportive medium; these differences are discussed.
5. Some characterizations of the isolated components are made.
The Effects of Components of Guinea Pig Serum on Lymphosarcoma 6C3HED in C3H Mice
Authors: HERBUT PETER A. , KRAEMER WILLIAM H. , PILLEMER LOUIS 
Published: October 2019

Abstract
The effects of various preparations of guinea pig serum on the Gardner lymphosarcoma 6C3HED in C3H mice were studied. Complete regression of tumor as well as marked retardation of growth were noted as a result of treatment with the following sera: (1) normal; (2) depleted of complement 1 (R1); of complement 3 (R3), and of complement 4 (R4); (3) depleted of properdin (RP); (4) heated at 56 C. for 20 minutes and for 60 minutes and at 66 C. for 30 minutes; and (5) supernatant from centrifuged at 35,000 G at 2 C. for 3 hours. No tumor inhibitory effect was noted as a result of treatment with (1) serum depleted of complement 2 (R2) and (2) pellet (containing lipopolysaccharides) from serum centrifuged at 35,000 G at 2 C. for 3 hours. These results indicate that the tumor inhibitory principle (TIP) in guinea pig serum is probably not complement, properdin, or lipopolysaccharide.
Properdin titers of sera from mice treated with each of the preparations listed above disclosed low properdin levels when the tumors were growing or were large, and normal or elevated properdin levels when the tumors were regressing or disappeared completely. In addition, normal nontumor-bearing mice showed as much as a threefold increase in properdin levels when treated with normal or heated guinea pig serum.
While it is possible that the tumor inhibitory principle (TIP) in guinea pig serum may exert its effect through the animal’s own properdin system, such a relationship has not as yet been demonstrated.
The Detection of Minor Erythrocyte Populations by Mixed Agglutinates
Authors: JONES A. RICHARDSON , SILVER SHEILA 
Published: October 2019

Abstract
The principle of the "mixed agglutination" reaction has been applied to the development of a technic for the detection of minor populations of erythrocytes in mixtures in which the minor component is identifiable by means of one or another of the blood group iso-antigens. The method lends itself to the quantification of a minor population and provides a degree of sensitivity which compares very favorably with that which can be achieved through the use of radioactive tracers.
Selenoid (Crescent) Bodies
Authors: Cuadra Manuel 
Published: October 2019

Abstract
Cuadra, Manuel: Selenoid (crescent) bodies. Blood 13:258-265 (March), 1958.
On p. 260, line 7, the statement is made:
"Selenoid bodies with their inseparable components of central vacuole (‘vesicle’) and pink crescent (‘lunula’) were found in small numbers in normal blood and occurred in very large numbers in cases of acute hemolytic anemias8; they are apparently related to the physiologic and pathologic destruction of erythrocytes."
The author desires it to read:
"The stromata of the erythrocytes appeared in the shape of a red disc and were clearly differentiated from erythrocytes; they were found in small numbers in normal blood and occurred in very large numbers in cases of acute hemolytic anemias8; they are apparently related to the physiologic and pathologic destruction of erythrocytes."
Ribosome Biosynthesis in Cultured Lymphocytes: II. The Role of Ribosomal RNA Production in the Initiation and Maintenance of Lymphocyte Growth
Authors: RUBIN ARNOLD D. 
Published: October 2019

Abstract
Ribosomal RNA production in cultured lymphocytes appeared to be regulated by the rate of 45S rRNA precursor transcription and also by the rate of 45S processing to the 28S and 18S components found in mature ribosomes. Cultures of resting lymphocytes restricted ribosome formation by maintaining both transcription and processing of 45S RNA at low levels. Still about 50 per cent of the RNA finally processed to 28S lacked corresponding 18S components as a result of selective degradation in resting lymphocytes. After PHA treatment, the rates of 45S rRNA precursor transcription and cleavage to 28S products, detectably increased within one hour, rose to a maximum at 48 hours. However, conservation of 18S components reached maximal efficiency between one to five hours after PHA treatment. By 48 hours, at the height of the growth response, PHA-stimulated cultures once again began to selectively degrade 18S RNA. At 168 hours, after the proliferative process had ceased, 45S processing slowed considerably despite a brisk rate of 45S RNA transcription —approximately 50-75 per cent of maximum.
Thus, the initiation of lymphocyte growth and the maintenance of the growing condition may depend on the rate of ribosome biosynthesis which, in turn, may be regulated by the efficiency of 45S rRNA precursor utilization for ribosome assembly.