bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Plasmacytoid Dendritic Cell like Leukemia Cell Line (PMDC05) Established from a Patient with CD4+CD56+ Acute Leukemia.
Authors: Narita Miwako , Tochiki Nozomi , Watanabe Norihiro , Saitoh Anri , Hashimoto Shigeo , Tsuchiyama Junjiro , Furukawa Tatsuo , Aoki Sadao , Fuse Ichiro , Aizawa Yoshifusa , Takahashi Masuhiro 
Published: April 2020

Abstract
Human dendritic cell precursors are commonly divided into two distinct subsets: myeloid DC and Plasmacytoid DC (pDC). The pDC, which show plasma cell like morphology, have been defined as the population that produce a large amount of type I interferon in response to viruses. The surface phenotypes of human pDCs are defined as CD4+, DC11c−, CD45RA+, IL3Rα (CD123)+, CD1c (BDCA-1)−, CD303 ((BDCA-2)+ and lineage negative. On the other hand, leukemia/lymphoma cells in CD4+CD56+ leukemia/lymphoma have been proposed to be of pDC lineage. CD4+CD56+ pDC leukemia/lymphoma are a rare hematological malignancy, totally only about 100 cases in the world by the literatures. We established a pDC like leukemia cell line (PMDC05) from leukemia cells of a patient with CD4+CD56+ acute leukemia. PMDC05 showed a complex hypoploid chromosomal abnormalities (44, XY) including add(5)(q22), add(15)(q26) and del(15)(q11q15), which is identical to original leukemia cells. Abnormalities including 5q and 15q are reported as the frequent aberrations in CD4+CD56+ pDC leukemia/lymphoma. PMDC05, which morphology was similar to plasma cells, was positive for CD4, CD56, CD123, CD33, CD86, HLA-ABC, HLA-DR, CD1a, CD40, and CD83 but negative for linage markers. Cytokine receptors for GM-CSF, IL3Rα and IL-6Rα were positive on PMDC05. The expression of Trail and Flt-3L was positive. By the culture with IL-3, CPG-A/B, GM-CSF, molecules associated with antigen presentation such as CD1a and CD40 were up-regulated. Besides, the addition of LPS increased the expression of CD40, CD80 and CD83 on PMDC05. PMDC05 by itself possessed a potent antigen presenting ability to naïve T cells and the treatment of PMDC05 with IL-3, CPG-A/B, or GM-CSF enhanced the antigen presenting ability to naïve T cells. TLR7, TLR 8 and TLR 9 as well as TLR1, TLR2, TLR4 were demonstrated to be expressed on PMDC05 by RT-PCR and RQ-PCR showed that the expression of TLR7 and TLR9 was most characteristic. λ-like 14.1 and preTα was also demonstrated to be expressed on PMDC05 by RT/RQ-PCR. PMDC05 possessed an ability to uptake the antigens like FITC-dextran and lucifer yellow. Although IFN-α was not identified to be secreted from PMDC05 by the stimulation of influenza virus, IFN-γ and TNF-α was demonstrated to be secreted to the similar level in pDC, which was examined simultaneously with PMDC05 by CBA assay. These data demonstrated that newly established leukemia cell line PMDC05 is involved in pDC lineage and PMDC05 provides invaluable tools not only for the elucidation of pathophysiology of CD4+CD56+ leukemia/lymphoma but also for the investigation of differntiation and regulation of pDC. In addition, PMDC05 could be applied for generating tumor-specific CTL clone, which may be used for anti-tumor cellular immunotherapy.
Expression of Activating Natural Killer Cell Receptor Ligands in Childhood Acute Lymphoblastic Leukemia.
Authors: Mura Ulrike , Pfeiffer Matthias , Handgretinger Rupert , Lang Peter J. 
Published: April 2020

Abstract
Activating and inhibitory cell surface receptors regulate natural killer (NK) cell effector functions. The extent of expression of their activating ligands on target cells probably plays a critical role in tumor immune surveillance, but the data of this expression on blasts of leukemia patients are still poor. We examined blasts of children with ALL for the activating human NKG2D ligands MICA, MICB, ULBP1, ULBP2 and ULBP3, and for the ligands of the activating human natural cytotoxic receptors (NCRs) NKp30, NKp44 and NKp46. Using ligand specific mouse monoclonal antibodies and flow cytometry, we screened 24 children (23 common-ALL, one pre-T-ALL) for the expression of NKG2D ligands and 15 children (all common-ALL) for NCR ligands. In 13 patients (all common-ALL), also the density of the NKG2D ligands was determined by quantitative flow cytometry. Considering cells positive for a particular ligand in case of a two fold increase of median fluorescence above negative control, 38 percent of the patients were positive for one or more NKG2D ligands, while only 13 percent expressed one or more NCR ligands at significant levels. ULBP1 was most frequently expressed (29 percent of patients positive), while no patients were positive for ULBP2 and NKp44 ligands. ULBP3 was positive in 17 percent of the patients, NKp30 and NKp46 ligands in 13 percent, MICA and MICB in 4 percent. The patient with pre-T-ALL was positive only for ULBP1. So ULBP1 was expressed more frequently, while the other NKG2D ligands were expressed less frequently in children than reported for adult leukemia patients before (Salih et al. Blood.2003;102:1389–1396.). The density of detected NKG2D ligand molecules was always rather low. For MICA the maximum were 1700 molecules per cell in a single patient, for MICB 900, for ULBP1 1100, and for ULBP3 1000 molecules per cell. In summary, blasts of pediatric ALL patients displayed low or negative surface levels of ligands for the human activating NK cell receptors NKG2D, NKp30, NKp44 and NKp46.
QUALITATIVE LIGAND EXPRESSION QUALITATIVE LIGAND EXPRESSION QUANTITATIVE LIGAND EXPRESSION QUANTITATIVE LIGAND EXPRESSION
Evolution of FLT3 Internal Tandem Duplication at the Diagnosis, Relapse, Remission or Induction Failure during the Treatment in Acute Myeloblastic Leukemia.
Authors: Bang Soo-Mee , Ahn Jeong Yeal , Park Jiyoon , Park Se Hoon , Nam Eun Mi , Cho Eun Kyung , Shin Dong Bok , Lee Jae-Hoon , Yoo Soo Jin , Jeon In Sang , Kim Yeo-Kyeoung , Kim Hyeoung Joon , Kim Hee-Nam , Lee Il-Kwon , Kang Hyoung Jin , Shin Hee Young , Ahn Hyo Seop 
Published: April 2020

Abstract
The FLT3 is class III fms-like tyrosine kinase. FLT3 mutations are one of the most frequent genetic changes at diagnosis and have been reported to be of prognostic significance in acute myeloid leukemia. FLT3 internal tandem duplication of the juxtamembrane domain (FLT3 ITD) was analyzed by PCR of genomic DNA at diagnosis or during the follow-up in patients with acute myeloid leukemia (AML). Total 223 patients were diagnosed as AML from Mar. 1996 till Aug. 2005. Their median age was 34 years-old (range: 0–86). The number of male or female patients was 116 or 107. Their FAB classifications were M0/1/2/3/4/5/6/7/RAEB/biphenotypic in 6/23/85/20/32/21/13/16/2/5 patients, respectively. Cytogenetic data at diagnosis were available in 182 patients; good/ intermediate/poor risk in 51/107/24 patients, respectively. Among the 190 patients receiving induction therapy, 147 patients achieved hematologic remission with a remission rate of 77%. Median event-free (EFS) and overall survival were 9 (95% confidence interval: 8–12) months and 14 (95% CI: 11–14) months, respectively. The incidence of FLT3 ITD at diagnosis was 13% (29/223). FLT3 ITD was more prevalent in M0~4 subtypes and older age. Among non-M3 population (N=203), patients with FLT3 ITD had a significantly short EFS when compared with those without ITD (p=0.0454). Among the 52 relapsed patients, 9 patients had a FLT3 ITD at diagnosis. Six patients showed reappearing of ITD and 3 patients remained negative at relapse. One patient acquired new ITD at relapse among 43 relapsed patients who had not baseline ITD. Tested 100 samples of 92 patients at remission were all negative for FLT3 ITD. Among the 28 patients at induction failure, one patient showed persistent ITD, one another re-appeared ITD after relapse, and the other one newly-developed ITD. Two others showed disappearance of ITD despite of persistent disease. Leukemic clones with FLT3 ITD may be susceptible to conventional chemotherapeutic agents and have no value for minimal residual disease. Therefore, effective induction and consolidation therapy could convert the poor prognosis of AML with FLT3 ITD.
Allosensitized Memory CD4 T Cells Induce Chronic Graft Versus Host Disease.
Authors: Dutt Suparna , Tseng Diane , George Tracy I. , Ermann Joerg , Liu Yinping , Fathman C. Garrison , Strober Samuel 
Published: April 2020

Abstract
It has been reported that naive CD4+CD62LhiCD44lo T cells induce severe GVHD in a complete MHC mismatched allogeneic model of mouse bone marrow transplantation (BMT), but that effector memory CD4+CD62LloCD44hi T cells obtained from normal donors do not induce GVHD. The lack of GVHD-inducing capacity of effector memory cells from unprimed donors may reflect their lack of previous exposure to host alloantigens. We tested this hypothesis in a complete MHC mismatched allogeneic model of BMT by comparing the ability of effector memory T cells obtained from untreated C57BL/6 donors and donors immunized against host BALB/C alloantigens to induce GVHD. C57BL/6 donors were immunized by injecting 50 x106 host BALB/C spleen cells i.p. and after one week with 10x 106 cells. Both the unprimed and alloantigen primed CD4+ T cells expressed similar levels of lymph node homing chemokine receptor CCR7, and activation markers like CD69 and CD25. We sorted naive (CD62LhiCD44lo) and effector memory (CD62LloCD44hi) CD4+ T cell subsets from C57BL/6 donor mice four weeks after immunization, and compared their alloreactivity to BALB/C in an in vitro MLR. Interestingly effector memory CD4+ T cells from primed mice produced significantly higher levels of IFNγ compared to the effector memory from unprimed donors. We found that CD62LloCD44hi cells from unimmunized donors failed to induce GVHD in 85% of the hosts over 100 days while CD62LloCD44hi cells from immunized donors caused progressive weight loss and death in 100% of hosts (p &lt;0.001). Whereas naive CD4+ T cells from unimmunized donors accumulated rapidly in the lymph nodes and spleen of irradiated hosts, effector memory CD4+ T cells had markedly reduced accumulation in these tissues. Furthermore, at day 6 after transplantation effector memory CD4+ T cells from primed mice, showed hundred fold higher accumulation in the host liver compared to unprimed effector memory donor CD4+ T cells. Long term surviving hosts transplanted with primed effector memory cells showed histopathological features of chronic GVHD in liver characterized by portal tract inflammation and lymphocyte infiltration with bile duct injury. In conclusion, memory CD4+ T cells from donors immunized to host alloantigens are able to induce chronic GVHD , but memory cells from unimmunized donors do not.
Knockdown of the Nuclear Oncogene SKI Inhibits Flt3-ITD Induced Signaling in 32D - Flt3-ITD Cells.
Authors: Hagner Nicole M. , Burchert Andreas , Eilers Martin , Neubauer Andreas 
Published: April 2020

Abstract
Ski is a nuclear oncogene implicated in repressing TGF-β signaling. Recently, we found that Ski is overexpressed in AML, especially in AML with deletion of chromosome 7 or 7q−. We also showed that Ski inhibits myeloid differentiation by preventing retinoic acid signaling in U937 cells. It is unclear, however, how Ski exerts its oncogenic effect in myeloid leukemia cells. In order to address this question, we took advantage of the factor-independent murine myeloid progenitor cell line 32D, which is rendered factor independent via expression of Flt3 internal tandem duplication (Flt-3-ITD). We found that Ski protein expression is upregulated in Flt3-ITD transfected 32D cells (32D-Flt3) when compared to vector transfected 32D control cells (32D-V). Ski upregulation is reversed by treatment with specific Flt3-ITD inhibitor PKC412. As Flt3-ITD transformation is known to mediate factor-independent activation of STAT5 we investigated STAT5 phosphorylation status in these cells after treatment with PKC412 or knockdown of Ski with specific siRNA targeted to murine Ski (mSki). As expected, expression of phosphorylated STAT5 (pSTAT5) as measured by Western blot and flow cytometry was strongly reduced after PKC412 treatment. Interestingly, a similar reduction of pSTAT5 expression was also achieved by siRNA treatment against mSki but was not seen in non-silencing siRNA treated 32D-Flt3 cells. In parallel, transfection of siRNA against mSki, but not of non-silencing RNA led to significant inhibition of cell proliferation in 32D-Flt3-ITD cells and to a much lesser extent in 32D-V- cells. Together, these data suggest that in in addition to AML with −7 / del7q, Ski may also be implicated in AML with Flt3-ITD, as it regulates Flt3-ITD induced STAT5 phosphorylation, which itself is a key transcription factor in leukemogenesis.
Hypoplastic Acute Myeloid Leukemia.
Authors: Park Hye-Won , Lee Je-Hwan , Choi Seong-Jun , Lee Jung-Hee , Seol Miee , Lee Young-Shin , Ryu Seong-Gil , Kim Keun Hee , Jang Seongsoo , Seo Eul-Joo , Park Chan-Jeoung , Chi Hyun-Sook , Lee Jung-Shin , Kim M. Wookun , Lee Kyoo Hyung 
Published: April 2020

Abstract
Hypoplastic variant of acute leukemia is rare and almost always has a myeloid phenotype. We retrospectively investigated the incidence, clinico-laboratory characteristics, and clinical outcomes of hypoplastic acute myeloid leukemia (HAML), which was defined by bone marrow hypocellularity (less than 40% of cellularity in trephine biopsy) with increase of bone marrow blasts (20% or more) and peripheral blood leukopenia (less than 4,000/μl). Between 1989 and 2005, 740 patients were diagnosed as having AML at the Asan Medical Center and the definition of HAML was satisfied in 24 (3.3%). Patients with HAML showed a higher median age (67.5 vs. 44.0 years; P&lt;0.001), a higher frequency of CD34 (100% vs 61.7%; P=0.007) and MDR (90% vs. 58%; P=0.043) expression and lower survival rate (6.7% vs 26.7% at 5-year; P=0.035) compared to other AML patients. The age range of 24 HAML patients, 16 males and 8 females, was 19 to 86 years, and 17 patients (70.8%) were 60 years or more. The results of cytogenetic analysis were available in 16 patients: 1 in good risk group, 14 in intermediate risk group, and 1 in poor risk group. Induction chemotherapy was given to 14 patients (58.3%): standard induction chemotherapy with AI or AD regimen (AI/AD) in 9 patients and low-dose cytarabine (LDAC) in 5. Complete remission (CR) was induced in 7 (50.0%) of 14 patients: 44.4% for AI/AD and 60.0% for LDAC. The CR rate was lower in patients with higher LDH over 400 U/L (25.0% vs. 100%; P=0.014). A median overall survival (OS) was 131 days. Seventeen patients died, two were lost to follow up, two were alive without disease, and one was alive with disease. Both patients, who were alive without disease, received allogeneic hematopoietic cell transplantation (HCT). Age (P=0.007) and LDH (P=0.016) were significant prognostic factors for OS. Our results suggest that HAML represents a poor prognostic group of patients. Prospective study is warranted for establishment of optimal treatment strategy including LDAC and HCT.
Obesity in Newly Diagnosed Childhood Acute Promyelocytic Leukemia.
Authors: Feusner James , Kim Haesook , Gregory John , Alonzo Todd , Woods William , Weinstein Howard , Tallman Martin 
Published: April 2020

Abstract
Obesity has been reported in several series of adults with acute promyelocytic leukemia (APL) (Estey et al., Leukemia11:1661–1664,1997; Douer et al.,Blood87:308–313,1996). Speculation regarding causation has included an association with female gender and/or an increased incidence of this disease in peoples of Latin extraction (Douer, Blood 1996). To date there have been no published reports of evaluation for obesity in children with APL. We report herein the results of an evaluation of body size of children enrolled on the first North American Intergroup trial of APL (INT 0129)(Tallman et al., N Engl J Med337:1021–1028,1997). This study was open for patient (pt) enrollment from April 1992 to February 1998. Fifty-three children (aged 1.4–18 years) with confirmed t (15;17) APL were eligible and evaluable. Body mass index (BMI) was calculated and compared to normals according to data from the 2000 CDC report (Ogden et al., Pediatrics 109:45–60,2002). Those pts who were obese (BMI &gt; 95th centile for age and gender) were compared to the others on this trial. Three pts were excluded: 2 were too young for BMI assessment (&lt; 2 years of age) and 1 insufficient body size data. Of the 50 evaluable pts, 26% (13/50) were obese. This compares to the expected overall incidence of 11% in the healthy pediatric population (Troiano et al., Pediatrics 101:497–504,1998). Comparisons of the obese pts to the rest on INT 0129 are shown:
Obese compared to non-obese pts Age (med) Sex Hispanic CR DFS-10 yr * Survival-10 yr * *Kaplan-Meier estimates Obese (13) 12.7 yrs 54% F 8% 85% 55% 77% Not Obese (37) 11.8 yrs 62% F 16% 84% 34% 57%
There were no statistically significant differences in CR (p&gt;0.99), DFS (p=0.56), or survival (p=0.31) between the obese and the non-obese. Our data confirm a higher than expected incidence of obesity in children with APL, as previously reported in some adult series. Although the number of pts is relatively small, there is no suggestion of an increased representation of females or Hispanics in this subgroup of APL. Also of interest, the outcomes for obese children in this trial were no worse than for the non obese. The association of obesity at diagnosis with APL appears to be a real one, and deserves confirmation via meta-analysis of other pediatric trials, and investigation as to possible causal links with APL.
Increased Risk of PICC Line Thrombosis in Acute Promyelocytic Leukemia.
Authors: Gatt Moshe E. , Levin Moshe 
Published: April 2020

Abstract
Introduction: Central venous access catheters are being used at increasing rates in the practice of hematology. Although significant complication rates in patients with solid tumors exist, studies have shown a lower incidence of complications in hematology patients. Recently, we noted an increased incidence of percutaneously inserted central catheters (PICC line) thrombosis in patients with acute promyelocytic leukemia (APL).
Methods: We undertook an evaluation of the medical records of all adult patients with acute leukemia (AL) from the year 1995 to 2005 at our two hematology centers. All indwelling catheters (of which most are PICC lines) at our institutions are inserted by interventional radiologists under fluoroscopic visualization. The catheters are flushed with saline and heparin prophylaxis was not routinely used during this evaluation period. All thrombotic episodes were diagnosed based on clinical and ultrasound duplex studies. Data was collected in reference to catheters, thrombotic and infectious complications, and relationship to diagnosis and treatment.
Results: Of 368 evaluated patients with a central venous catheter and AL, there were 23 incidents of clinically apparent catheter thrombosis (6.2%). The subgroup incidence of catheter thrombosis was nine of 237 (3.8%) patients with acute myelogenous leukemia not including APL (AML), seven of 104 patients (6.7%) with acute lymphoblastic leukemia (ALL), half of the ALL episodes were associated with catheter sepsis, and seven of 25 (28%) with APL. Comparison of the APL group with the AML group is significant at p &lt; 0.03.
Conclusion: There appears to be an increased incidence of PICC line thrombosis in APL patients. This may be secondary to the institution of all trans retinoic acid (ATRA) treatment and the thrombophillia of APL. In ALL patients the slightly raised incidence may be due to the thrombophillia of asparaginase or the increased infectious complications of high dose steroids associated with ALL treatment. Based on these findings we would recommend heparin prophylaxis for APL patients with central venous access lines. Following this evaluation we instituted heparin prophylaxis for newly diagnosed APL patients and found no evidence of clinically apparent thrombosis in 8 consecutive patients. There were no episodes of increased bleeding in these 8 APL patients. Further analysis of the data will be presented.
Clinical Significance of Free Circulating CD33 in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome.
Authors: Hodge Menna , Giles Francis , Abdool Adam , O’Brien Susan , Keating Michael , Jilani Iman , Estrov Zeev , Estey Elihu , Kantarjian Hagop , Albitar Maher 
Published: April 2020

Abstract
CD33, a 67-kDa sialoglycoprotein expressed on the cell surface of monocytic/myeloid lineage and early hematopoietic progenitor cells, is frequently expressed in patients with acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO), an immunoconjugate consisting of a humanized anti-CD33 antibody and a cytotoxic compound (N-acetyl-γ-calicheamicin dimethylhydrazine), targets CD33 and has shown promising results in patients with AML. No evidence of a relationship between the levels of CD33-positive leukemic cells and clinical response has been found. We investigated the possibility that cell-free circulating CD33 (cCD33) might be useful as a marker of clinical behavior. We used a newly developed bead-based immunoassay to measure cCD33 in the plasma of patients with AML (n = 97) or myelodysplastic syndrome (MDS; n = 44). All patients were treated with standard therapy including idarubicin and ara-C. cCD33 levels were significantly higher in patients with MDS (median, 1600 U/μL; range, 102–791,350 U/μL) than in those with AML (median, 2709 U/μL; range: 62–263,349 U/μL) (P = 0.004). High-risk cytogenetic abnormalities were associated with higher cCD33 levels in patients with MDS (P = 0.04) but not in patients with AML (P = 0.72). cCD33 levels correlated with WBC count and % monocytes in patients with AML (R &gt;0.35) but not in patients with MDS. cCD33 levels correlated with clinical behavior only among AML patients with intermediate-risk cytogenetic abnormalities (n = 56); those with cCD33 levels above the median had longer survival (P = 0.04). These data confirm the presence of cCD33 in AML and MDS and also suggest that cCD33 can be used as a tumor marker in patients with AML. Although further study is needed for confirmation, cCD33 appears to result from turnover of leukemic cells, may play a role in patients being treated with GO, and should be considered in the pharmacokinetic and pharmacodynamic studies of such therapy.
cCD33 in AML patient with intermediate cytogenetic abnormalities cCD33 in AML patient with intermediate cytogenetic abnormalities