Rojin Park

Rare translocations involving chromosome band 8p11 in myeloid neoplasms.

Two types of distinct clinical syndromes are associated with abnormalities of chromosomal band 8p11 [1]. The first is 8p11 myeloproliferative syndrome (EMS)estem cell leukemia-lymphoma syndrome (SCLL), an aggressive chronic myeloproliferative disorder characterized by myeloid hyperplasia, eosinophilia, and lymphoblastic lymphoma. The second clinical syndrome is an acute myeloid leukemia (AML) of monocytoid phenotype (FAB type M4 or M5) with erythrophagocytosis. The abnormalities of chromosome band 8p11 target two different genes, FGFR1 in EMS and MYST3 (alias MOZ ) in AML. Rosati et al. [2] reported NSD3 (nuclear receptor-binding su(var)3-9, enhancer of zeste, trithorax [SET] domain containing gene 3) as the third translocation target in chromosome 8p11wp12 region, which is telomeric to FGFR1. (Note that NSD3 has since been classified as WHSC1L1; accession no. AF_332469.) Here, we report two rare translocations involving chromosome band 8p11 in myeloid neoplasms: t(8;22)(p11;q11) and t(8;11)(p11;p15). The first patient was a 50-year-old Korean woman, with no relevant past history, who presented with general weakness. An initial complete blood count showed a hemoglobin level of 9.5 g/dL, a platelet count of 596,000/mL, and a white blood cell count of 51,630/mL with 1% myeloblasts, 1% promyelocytes, 5% myelocytes, 6% metamyelocytes, 78% neutrophils, 4% lymphocytes, 1% monocytes, 2% eosinophils, and 2% basophils. A subsequent bone marrow biopsy revealed hypercellular marrow (O90%) with 18% blast cells and eosinophilia. An initial diagnosis of chronic myelogenous leukemia (CML), accelerated phase (AP), was made; however, the results of reverse transcriptasee polymerase chain reaction analysis (RT-PCR) for both major and minor BCReABL were negative. Three months later, transformation to blast phase (BP) occurred and the patient died of sepsis. The second patient was a 37-year-old Korean woman who was admitted with a complaint of abdominal pain and fever. She had been diagnosed with left-side breast cancer 11 years before and underwent a modified radical mastectomy. The patient was subsequently treated with chemotherapy and radiotherapy, when multiple metastases had developed. On presentation at our institution, many abnormal blasts (69%) were observed in the peripheral blood smear. An ensuing bone marrow aspiration revealed

Acute erythroleukemia with der(1;7)(q10;p10) as a sole acquired abnormality after treatment with azathioprine

To our knowledge, at least 11 different unbalanced wholearm translocations including der(1;7)(q10;p10), der(1;15) (q10;q10), der(1;16)(q10;p10), and der(1;19)(q10;p10) have been reported in hematologic malignancies, and some whole-arm translocations have now been documented as primary changes associated with specific disease entities [1e4]. Among these whole-arm translocations, der(1;7) (q10;p10) is the karyotypic aberration most associated with a previous history of chemotherapy or radiation therapy (i.e., in more than half the cases). This aberration is extremely rare, however, in association with acute erythroleukemia (AMLM6); only three cases have been reported in the literature [1,5e7]. Here, we report on a novel case of AML-M6 with der(1;7)(q10;p10) as a sole acquired abnormality in a patient treated with azathioprine for a long duration. A 64-year-old Korean woman with edema and suspected cellulitis of her right third finger was admitted to Severance Hospital of Yonsei University in February 2008. During her hospitalization, she sustained severe neutropenia. Approximately 2 weeks later, a gradual increase in immature cells in the peripheral blood smear compelled us to perform a bone marrow examination. In bone marrow aspiration, erythroid hyperplasia was observed (O50% of all nucleated cells) with abnormal blasts, which constituted 44% of nonerythroid cells, consistent with a morphology of AML-M6 with multilineage dysplasia. The patient exhibited an unbalanced translocation between the whole arms of chromosomes 1 (long arm) and 7 (short arm); the detailed karyotype of this patient was 46,XX,þ1,der(1;7)(q10;p10),inv(9)(p11q13)c in 20 cells analyzed (Fig. 1). Fluorescence in situ hybridization (FISH) analysis for chromosome 7 (Vysis LSI D7S486 (7q31), SpectrumOrangeeCEP 7 SpectrumGreen probe set; Abbott Molecular, Des Plaines, IL) yielded nuc ish (D7S486 1),(CEP7 2)[249/ 300]. Thus, the FISH results were consistent with the cytogenetic karyotype. The patient was treated with fludarabine, cytarabine, and idarubicin, but failed to achieve remission and died of pulmonary hemorrhage and septic shock 38 days after the initial diagnosis of AML-M6. In 1989, the patient had been diagnosed with idiopathic hypereosinophilic syndrome and vasculitis, and was treated

Comparison of Prothrombin Time Derived From CoaguChek XS and Laboratory Test According to Fibrinogen Level

CoaguChek XS is one of the most widely used point‐of‐care (POC) devices to evaluate prothrombin time for monitoring oral anticoagulant therapy. Unlike laboratory methods, it detects electrical signals produced by thrombin activity to derive the international normalized ratio (INR). Therefore, we hypothesized that laboratory methods and CoaguChek XS could produce different results according to fibrinogen level.

MLL rearrangement with t(6;11)(q15;q23) as a sole abnormality in a patient with de novo acute myeloid leukemia: conventional cytogenetics, FISH, and multicolor FISH analyses for detection of rare MLL-related chromosome abnormalities

We report a rare case of acute myeloid leukemia (AML) with t(6;11)(q15;q23) in a 50-year-old female showing a poor prognosis. Bone marrow biopsy revealed markedly hypercellular marrow with infiltrates of myeloblasts, consistent with AML-M2 morphology. The karyotype of this patient was 46,XX,t(6;11)(q15;q23) in all analyzed cells, and the results of fluorescence in situ hybridization (FISH) and multi-color FISH analysis confirmed this unique MLL rearrangement as a sole abnormality. To our knowledge, t(6;11)(q13 approximately q15;q23) is the most rare type of MLL rearrangement involving the long arm of chromosome 6. Only two cases with t(6;11)(q13;q23) and three cases with t(6;11)(q15;q23) have been reported, but detailed clinical or laboratory data were not available. From this report, it is apparent that in a cytogenetic laboratory, the accurate detection of a rare type of MLL rearrangement is very important in the differential diagnosis, prompt treatment, and prediction of prognosis of leukemias.

Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis

Background In sepsis, large scale inflammatory responses can cause extensive collateral damage to the vasculature, because both coagulation and fibrinolysis are activated unevenly. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in modulating fibrinolysis. Since TAFI can be activated by both thrombin and plasmin, it is thought to be affected in sepsis. Hence, activated and inactivated TAFI (TAFIa/ai) may be used to monitor changes in sepsis. Methods TAFIa/ai-specific in-house ELISA can detect only the TAFIa/ai form, because the ELISA capture agent is potato tuber carboxypeptidase inhibitor (PTCI), which has selective affinity towards only the TAFIa and TAFIai isoforms. TAFIa/ai levels in plasma from 25 patients with sepsis and 19 healthy volunteers were quantitated with the in-house ELISA. Results We observed increased TAFIa/ai levels in samples from patients with sepsis (48.7±9.3 ng/mL) than in samples from healthy individuals (10.5±5.9 ng/mL). In contrast, no difference in total TAFI concentration was obtained between sepsis patients and healthy controls. The results suggest that TAFI zymogen was activated and that TAFIa/ai accumulated in sepsis. Conclusion The detection of TAFIa/ai in plasma could provide a useful and simple diagnostic tool for sepsis. Uneven activation of both coagulation and fibrinolysis in sepsis could be caused by the activation of TAFI zymogen and elevation of TAFIa/ai. TAFIa/ai could be a novel marker to monitor sepsis and other blood-related disturbances.

Comparison of total and IgG ABO antibody titers in healthy individuals by using tube and column agglutination techniques.

Background Most immune reactions related to transfusion and transplantation are caused by IgM ABO antibodies. However, IgG also plays an important role in these reactions. Therefore, a method to measure antibodies, including IgG, is necessary. We investigated ABO antibody titers of healthy individuals using a column agglutination technique (CAT) with or without dithiothreitol (DTT) and compared them with titers obtained using a conventional tube method. Methods Among healthy adults who underwent a medical examination, 180 individuals (60 with blood group A, 60 with group B, and 60 with group O) were selected. Antibody titrations were performed using the immediate spin (IS) tube, anti-human globulin (AHG) tube, and CAT with or without DTT methods. Results Higher median values of anti-B and anti-A titers in groups A and B individuals, respectively, were obtained using the IS method than using the AHG method. Higher values for group O individuals were obtained using the AHG method. Higher median titers of anti-B and anti-A in group O individuals were obtained using CAT without DTT than using the AHG method. Median titers of anti-B and anti-A in all blood groups were higher in CAT without DTT than in CAT with DTT, especially for group O individuals. Conclusions We recommend CAT with and without DTT for titration of anti-A and anti-B, especially in group O individuals, to provide more sensitive results that include IgG data. Adjustment of insurance coverage of fees associated with antibody titration might be necessary, considering the actual cost of reagents and personnel.

An engineered fibrinogen variant AαQ328,366P does not polymerise normally, but retains the ability to form α cross-links

A fibrin clot is stabilised through the formation of factor XIIIa-catalysed intermolecular ε-lysyl-γ-glutamyl covalent cross-links between α chains to form α polymers and between γ chains to form γ dimers. In a previous study we characterised fibrinogen Seoul II, a heterozygous dysfibrinogen in which a cross-linking acceptor site in Aα chain, Gln328, was replaced with Pro (AαQ328P). Following on the previous study, we investigated whether the alteration of Gln residues Aα328 and Aα366 affects fibrin polymerisation and α chain cross-linking. We have expressed three recombinant fibrinogens: AαQ328P, AαQ366P, and AαQ328,366P in Chinese hamster ovary cells, purified these fibrinogens from the culture media and performed biochemical tests to see how the introduced changes affect fibrin polymerisation and α chain cross-linking. Thrombin-catalysed fibrin polymerisation of all variants was impaired with the double mutation being the most impaired. In contrast, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis showed α polymer formation with all three engineered proteins. This study demonstrates that AαQ328 and AαQ366 are important for normal fibrin clot formation and in the absence of residues AαQ328 and AαQ366, other Gln residues in the α chain can support FXIIIa-catalysed fibrin cross-linking.

A Case of Central Nervous System Myelomatosis with Complex Chromosome Aberrations

Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later, the patient expired.

Activities of Quality Improvement for Blood Culture at a University Hospital

Background: Blood culture is a critical test for diagnosing bloodstream infections. Frequent microbial contamination during sampling and testing leads to abuse of antimicrobial agents. We evaluated methods for reducing contamination and obtaining more reliable results. Methods: We analyzed blood cultures obtained between 2009 and 2015. We established 6 quality indicators: true positive rate, contamination rate, blood sampling volume, number of sets of blood cultures, delayed transportation rate, and percentage of samples collected from the femoral region, with reference to the CLSI guideline M47-A, 2007. Education was provided for interns and nurses responsible for blood sampling and transportation of specimens, and data were analyzed monthly. Results: At baseline, the true positive rate was 12.8%, and the contamination rate was 4.0%. During the intervention period, these were decreased to 10.9% and 1.9%, respectively. The percentage of samples smaller than 5 mL decreased from 29.7% to 2.711.3%. The rate of one set of blood cultures being ordered was always <5%. The delayed transportation rate decreased from 35.6% to 5.5-7.7%. Finally, the percentage of samples collected from the femoral region decreased from 41.5% to 22.0-31.0%, because of which we did not attain our goal, 20.8%. Conclusion: The results showed improvements in contamination rate, specimen volume, specimen transportation time, and the percentage of samples collected from the femoral region. The quality management of blood cultures in 2011 was comparatively poor, which led to increased contamination rate, large number of samples containing <5 mL of blood, and increased percentage of samples collected from the femoral region. Thus, quality improvement methods can produce more reliable results of blood cultures. (Ann Clin Microbiol 2015;18:88-93)

Evaluation of OraQuick Advance Rapid HIV-1/2 Antibody Test as a Screening Test for HIV Infection

Background: For the diagnosis of HIV infection, enzyme immunoassay (EIA) or chemiluminescence immunoassay (CLIA) is commonly used as a screening test. Although these methods have a high sensitivity and low cost, their high false positive rate can cause confusion in the patients and clinicians until a more specific test is done. OraQuick Advance Rapid HIV-1/2 Antibody Test (OraQuick) (OraSure Technologies, USA) is a rapid test that can detect HIV-1/2 antibodies in 20 minutes. It uses oral fluid, whole blood or serum sample. In this study, we evaluated the usefulness of the OraQuick as a screening and point-of-care test for HIV infection. Methods: From Jan 2007 to Dec 2008, 45,276 samples referred to our laboratory were tested by CLIA method using the ADVIA Centaur (Bayer Healthcare LTD., USA) for HIV-1/2 antibody detection. Among them, 74 positive and 50 negative samples were tested by the Western immunoblot assay (WIB) and OraQuick test as a case-control study. Also, oral fluids from 30 HIV patients and 48 healthy persons were tested by OraQuick test. Results: The sensitivity and specificity of OraQuick test (using serum samples) were 100% and 98.8% (95% confidence interval 96.9∼100%), respectively. OraQuick tests (using oral fluid samples) were all positive for HIV patients but all negative for healthy persons. Conclusion: This study suggests that OraQuick can be used successfully as a rapid test for the early detection of HIV-1/2 antibody in patients visiting emergency departments and for the prevention of HIV infection in the health care providers. (Korean J Clin Microbiol 2009;12:116-121)