Jaewoo Song

Delta neutrophil index: a promising diagnostic and prognostic marker for sepsis

ABSTRACT Delta neutrophil index (DN) is the immature granulocyte fraction provided by a blood cell analyzer (ADVIA 2120; Siemens Healthcare Diagnostics, Deerfield, Ill), which is determined by subtracting the fraction of mature polymorphonuclear leukocytes from the sum of myeloperoxidase-reactive cells. The purpose of this study was to define the role of DN in differential diagnosis and prognosis prediction of patients with sepsis. Hospital records of 273 patients were retrospectively collected: 47 with systemic inflammatory response syndrome, 78 with sepsis, 51 with severe sepsis, and 97 control subjects. Delta neutrophil index and C-reactive protein data on the day of the first blood culture were compared among the groups, and 28-day mortality associated with sepsis was assessed. Median values of DN were 0.0% (interquartile range, 0.0%–0.0%) in the control group, 0.8% (0.0%–1.7%) in the systemic inflammatory response syndrome group, 3.4% (1.5%–5.3%) in the sepsis group, and 18.6% (9.3%–24.7%) in the severe sepsis group. Furthermore, there were significant differences among the groups. The receiver operating characteristic curves showed that DN was a better predictor of sepsis than C-reactive protein. The best cutoff value for DN for predicting sepsis was 2.7%. Delta neutrophil index was significantly higher in those who died than in the survivors (median [interquartile range], 11.5% [3.5%–25.0%] vs. 4.7% [2.2%–10.6%], P = 0.008) and was identified to be an independent predictor for 28-day mortality in patients with sepsis by Cox proportional hazards model. Delta neutrophil index may serve as a facile and useful marker for early diagnosis and prognostic assessment of patients with sepsis, as it is included in a routine complete blood count.

Synthesis of ZSM-5 zeolite composite membranes for CO2 separation

ZSM-5 type zeolites were synthesized by the hydrothermal treatment of the reaction mixture of silica sol, aluminum nitrate, sodium hydroxide, and TPABr at the temperature range of 150–180 °C in the autoclave. The shape of the ZSM-5 zeolite calcined at 450 °C was spherical or polyhedral and its crystalline size was 0.5–3 μm. The synthetic ZSM-5 was found to be highly hydrophobic and active for CO2 adsorption. ZSM-5 zeolite composite membranes supported with porous α-alumina tubes have been synthesized by dip coating or pressurized coating of the reaction sol-mixture followed by hydrothermal treatment. The permeation mechanism of CO2 through ZSM-5 membranes was a surface diffusion and the membranes prepared by the pressurized-coating hydrothermal treatment showed a fairly high CO2/N2 separation factor of 9.0 and a permeability of 10−8–10−7 mol/m2 ·s·Pa at room temperature.

Acute promyelocytic leukemia with insertion of PML exon 7a and partial deletion of exon 3 of RARA: a novel variant transcript related to aggressive course and not detected with real-time polymerase chain reaction analysis.

We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinct breakpoint cluster region 2 (bcr2) variant transcript. Findings from bone marrow, cytogenetic, fluorescence in situ hybridization, and qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were consistent with the diagnosis of APL. Although PCR products of size 841 bp and 984 bp were amplified from bone marrow specimen, the quantitative PCR (RQ-PCR) findings were negative. Given the discrepancy in PCR results, sequencing of PCR products was performed to determine the detailed composition of these fusion transcripts. By cloning and sequencing, we discovered that these two bands were isoforms, in which one exon (exon 5, 144 bp) of the PML gene was spliced out of the smaller products (minor PCR products); one sequence (G) insertion and one base substitution (T-->C) of PML exon 4 generate a stop codon in the smaller fusion transcript. In addition, a search of the Ensembl database revealed that these variant PML/RARA fusion transcripts were composed of exon 7a insertion of the PML gene and partial deletion (46 bp) of exon 3 of the RARA gene, in addition to inserted sequences of intron 7 of PML and genomic sequence ATCT of unknown origin at the fusion junction site. Although the biological significance of most atypical transcripts remains unclear, sequence analysis of these atypical products should be performed, to reveal the composition of such a fusion transcript and elucidate the molecular mechanism.

Acute promyelocytic leukemia relapsing as secondary acute myelogenous leukemia with translocation t(3;21)(q26;q22) and RUNX1–MDS1–EVI1 fusion transcript

Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by peculiar clinical and biologic features, including severe hemorrhagic diathesis, specific recurrent chromosomal aberration, and distinct morphologic features with predominant pathologic promyelocytes. A reciprocal translocation involving chromosomes 15 and 17, t(15;17)(q22;q21), is a characteristic feature of APL that represents approximately 5-8% of AML. The rearranged gene created by this translocation encodes a chimeric protein PML-RARA that is a transcriptional repressor. In contrast to other AML subtypes, APL is particularly sensitive to treatment with all trans-retinoic acid (ATRA) combined with chemotherapy, converting this once fatal leukemia to a highly curable disease. Nonetheless, therapy-related myelodysplastic syndrome-acute myelogenous leukemia (t-MDS/AML) has been reported as a rare complication of chemotherapy in APL. Of 30 APL cases described as t-MDS/AML in the literature, only 1 case relapsed as acute leukemia with t(3;21)(q26;q22). Here we describe a rare case of APL relapsing as secondary AML with t(3;21)(q26;q22) and clinically characterize this patient using the RUNX1 (previously AML1)-MDS1-EVI1 fusion transcript (with follow-up for 55 months), and review the relevant literature.

JAK2 V617F/C618R mutation in a patient with polycythemia vera: a case study and review of the literature.

The acquired Janus kinase 2 (JAK2) V617F mutation shows a high frequency in diverse BCR/ABL-negative chronic myeloproliferative disorders (CMPD), and it is typically associated with polycythemia vera (PV). The frequency of JAK2 V617F mutation is about 90% in patients with PV, 50-60% in patients with essential thrombocythemia (ET), primary myelofibrosis (PMF), and less in patients with other myeloid neoplasms, while extremely rare in lymphoid malignancies. About 20 kinds of novel mutations of JAK2 other than V617F have been reported recently in the literature. Among these mutations, only one case of JAK2 V617F/C618R has been reported in a 67-year-old patient with PV. Here, we report a rare case of JAK2 V617F/C618R in a 41-year-old Korean male patient with review of the relevant literature on JAK2 mutations other than V617F. Although the frequency of JAK2 mutations other than the V617F is very low, this study emphasizes the need for assiduous analysis of the JAK2 gene to characterize new mutations, to determine their frequency, and to improve understanding of the clinical phenotypes as well as prognostic and biologic features associated with these mutations.

Preceding orbital granulocytic sarcoma in an adult patient with acute myelogenous leukemia with t(8;21): a case study and review of the literature

A 25-year old man with a 30 month history of proptosis and pain of the right eye was referred to Severance Hospital of Yonsei University. Orbital computed tomography (CT) demonstrated a huge mass in the right retrobulbar orbit; an incisional biopsy and orbitotomy were performed for diagnosis and orbital soft tissue decompression. Subsequent histopathology disclosed sheets of mononuclear cells in the orbital mass, and immunohistochemical stains demonstrated positive results for myeloperoxidase and CD43, which supported the diagnosis of granulocytic sarcoma (GS). After his 1-year follow-up, the patient presented with pancytopenia, and an ensuing bone marrow aspiration revealed markedly hypercellular marrow replaced by many large abnormal myeloblasts. The patient was diagnosed with acute myelogenous leukemia with t(8;21) preceded by orbital GS. Orbital GS is primarily a disease of children, and extremely rare in adults. To the best of our knowledge, only four cases of this disease in adults have been reported in the literature. Our case is the first report of preceding orbital GS in an adult patient with a complex karyotype including t(8;21).

Immature platelet fraction in diabetes mellitus and metabolic syndrome

INTRODUCTION Dysregulated platelet-endothelial interaction plays a pivotal role in atherothrombotic events in patients with diabetes mellitus (DM). Immature platelet fraction (IPF) is a hematologic parameter of automated hematologic analyzer and is related to platelet size and cytoplasmic RNA contents. It reflects thrombopoiesis and also is often used as the marker of platelet activity. MATERIAL AND METHODS We compared peripheral blood IPF, IPF count (IPC), and mean platelet volume (MPV) of DM and metabolic syndrome (MetS) patients with those of healthy controls. The IPF, IPC, MPV, and other blood cell indices were measured. RESULTS The DM group had significantly higher IPF (2.20 vs. 1.70%, P=.020), IPC (4.80 vs. 4.60×10(9)/L, P=.043), and MPV (10.35 vs. 10.00fL, P=.012) than the control group. Those markers were also increased in MetS patients, but the differences were not statistically significant. Interestingly, when DM patients were stratified according to glycemic control status (≤6.5% HbA1c vs. 6.6-7.9% HbA1c vs. ≥8% HbA1c), both IPF and IPC were significantly increased in poor glycemic control group (P=.014 and .003). Including various diabetic complications in the analysis, IPF was higher in DM patients complicated by cardiovascular disease than the DM group without cardiovascular disease. CONCLUSION IPF is elevated in patients with diabetes and associated with poor glycemic control and cardiovascular complication.

Detection of FUS-ERG chimeric transcript in two cases of acute myeloid leukemia with t(16;21)(p11.2;q22) with unusual characteristics

Reciprocal t(16;21)(p11;q22) is a rare chromosomal abnormality in acute myeloid leukemia (AML). The chimeric transcript FUS-ERG formed by this translocation which causes the replacement of RNA-binding domain of FUS (alias TLS) with the DNA-binding domain of ERG, and this event is thought to be responsible for leukemogenesis. Here we report two cases of AML with t(16;21)(p11.2;q22) showing unusual characteristics, and address the clinical, hematological, and molecular aspects of leukemia with t(16;21), along with a review of the literature.

Automated Detection of Malaria-Associated Pseudoeosinophilia and Abnormal WBC Scattergram by the Sysmex XE-2100 Hematology Analyzer: A Clinical Study with 1,801 Patients and Real-Time Quantitative PCR Analysis in Vivax Malaria-Endemic Area

Recently, the XE-2100 hematology analyzer was investigated in a rather small patient group; pseudoeosinophilia or abnormal white blood cell (WBC) scattergrams reported by this instrument were considered as significantly valuable diagnostic parameters in detecting vivax malaria. This study was conducted not only to assess the usefulness of pseudoeosinophilia or abnormal WBC scattergram in vivax malaria-endemic areas with large patient groups (N = 1,801) but also to investigate the correlation of parasitemia and platelet count with pseudoeosinophilia and abnormal WBC scattergrams. Of the 1,801 analyzed patients, 413 (22.9%) were found to have malaria by Wright-Giemsa stained blood smears. Overall, either pseudoeosinophilia or abnormal WBC scattergram was detected in 191 of 413 malaria patients and 4 of 1,388 patients without malaria (sensitivity = 46.2%, specificity = 99.7%). We suggest that clinical hematology laboratories using the XE-2100 analyzer should be aware of such specific parameters, even with the absence of a clinical request.

Molecular characterization of alternative SET-NUP214 fusion transcripts in a case of acute undifferentiated leukemia

Cryptic deletions are occasionally reported in hematologic malignancies. The SET-NUP214 fusion gene has been rarely reported in acute myeloid leukemia, acute undifferentiated leukemia, and recurrently in T-cell acute lymphoblastic leukemia. The fusion product is generated by a submicroscopic deletion in the vicinity of 9q34. Herein we present a novel case of acute undifferentiated leukemia with SET-NUP214 rearrangement due to the cryptic deletion of the 9q34 region producing two different types of fusion transcripts by alternative splicing and molecular characterization of the fusion transcripts by fluorescence in situ hybridization, reverse transcriptase-polymerase chain reaction, and array comparative genomic hybridization analyses.