Hyeon-Ho Lim

Platelet Function Analyzer-200 P2Y Results Are Predictive of the Risk of Major Adverse Cardiac Events in Korean Patients Receiving Clopidogrel Therapy Following Acute Coronary Syndrome

Background Clopidogrel is one of the most commonly used anti-platelet agents in cardiovascular diseases. We analyzed the relationship between the platelet function analyzer (PFA)-200 P2Y (INNOVANCE PFA-200 System, Siemens Healthcare, Germany) results and occurrence of major adverse cardiac events (MACEs) in Korean patients with recent-onset acute coronary syndrome (ACS) taking clopidogrel. Methods Between August 2013 and June 2016, we prospectively enrolled 106 patients with recent-onset ACS who had been treated with clopidogrel. We obtained blood samples and measured closure time (CT) using the PFA-200 P2Y test. Patients were divided into two groups on the basis of a CT cut-off value of 106 seconds. We compared patient characteristics and various MACEs that occurred during the follow-up period. Results The CTs for 78 patients exceeded the cut-off value. At the time of these analyses, 11 patients had been diagnosed with MACEs. In the time-to-event analysis, there was a difference between the two groups (P<0.001). After adjusting other variables associated with MACE occurrence, CT value was the strongest predictor of MACEs, with a 7.30-fold occurrence risk (P=0.002). Conclusions We found a strong relationship between CT and MACE risk in Korean patients with recent-onset ACS taking clopidogrel. Accordingly, PFA-200 P2Y results could be used as a predictive marker for MACE risk in such patients.

Philadelphia-positive mixed phenotype acute leukemia presenting with PML-RARα fusion transcript without t(15;17) on cytogenetic studies

REFERENCES 1. Lee JY, Lee SM, Yoon HK, Kim KH, Choi MY, Lee WS. A case of synchronous multiple myeloma and chronic myeloid leukemia. Blood Res 2017;52:219-22. 2. Thomas A, Mailankody S, Korde N, Kristinsson SY, Turesson I, Landgren O. Second malignancies after multiple myeloma: from 1960s to 2010s. Blood 2012;119:2731-7. 3. Wolleschak D, Heidel FH. Chronic myelogenous leukemia evolving after treatment of multiple myeloma. Blood 2016;128:146. 4. Alsidawi S, Ghose A, Qualtieri J, Radhakrishnan N. A case of multiple myeloma with metachronous chronic myeloid leukemia treated successfully with bortezomib, dexamethasone, and dasatinib. Case Rep Oncol Med 2014;2014:962526. 5. Pessach I, Bartzis V, Tzenou T, et al. Multiple myeloma and chronic myelogenous leukemia; an uncommon coexistence in 2 patients, with literature review. Ann Hematol Oncol 2015;2: 1030. 6. Nakagawa M, Noto S, Kobayashi H, Hayashi M. A case of a 47 year old man who developed chronic myelogenous leukemia after therapy for multiple myeloma. J Obihiro Kosei Gen Hosp 2003;6:101-6. 7. Nitta M, Tsuboi K, Yamashita S, et al. Multiple myeloma preceding the development of chronic myelogenous leukemia. Int J Hematol 1999;69:170-3. 8. Klenn PJ, Hyun BH, Lee YH, Zheng WY. Multiple myeloma and chronic myelogenous leukemia-a case report with literature review. Yonsei Med J 1993;34:293-300. 9. MacSween JM, Langley GR. Light-chain disease (hypogammaglobulinemia and Bence Jones proteinuria) and sideroblastic anemia-preleukemic chronic granulocytic leukemia. Can Med Assoc J 1972;106:995-8. 10. Ragupathi L, Najfeld V, Chari A, Petersen B, Jagannath S, Mascarenhas J. A case report of chronic myelogenous leukemia in a patient with multiple myeloma and a review of the literature. Clin Lymphoma Myeloma Leuk 2013;13:175-9. Philadelphia-positive mixed phenotype acute leukemia presenting with PML-RAR fusion transcript without t(15;17) on cytogenetic studies

NUP98 Rearrangement in Acute Myelomonocytic Leukemia With t(11;19)(p15;p12): The First Case Report Worldwide

Dear Editor, AML is a group of heterogeneous diseases derived from various cytogenetic and molecular abnormalities that are significant for diagnosis, treatment, and prognosis in many cases. We report a rare case of AML harboring t(11;19)(p15;p12) that was detected with whole-genome sequencing (WGS). A 33-yr-old woman was admitted to a local hospital with abdominal pain and diarrhea for five days. After conservative treatment, the symptoms improved. However, definite leukocytosis persisted; therefore, the patient visited our hospital for further evaluation. The initial complete blood count showed an Hb level of 7.6 g/dL, white blood cell (WBC) count of 29.48×10/L, and platelet count of 53×10/L. On the peripheral blood smear, differential counts revealed 15% segmented neutrophils, 16% lymphocytes, 60% monocytes, 1% eosinophils, 1% atypical lymphocytes, 1% promyelocytes, 6% blasts, and 4 nucleated red blood cells (RBCs) per 100 WBCs. RBCs were macrocytic and hyperchromic with mild polychromasia and anisocytosis. The bone marrow (BM) aspirate smear showed increased myeloblasts and monoblasts (7.6% and 42.0% of all nucleated cells, respectively) (Fig. 1A). Some blasts were positive for myeloperoxidase (MPO), Sudan black B, specific esterase, and non-specific esterase stains, and showed fine granular positivity for periodic acid-Schiff stain. BM biopsy revealed a markedly hypercellular marrow (95–100% cellularity) with infiltrations of leukemic blasts. Flow cytometric analysis revealed the blasts to be positive for CD11c, CD14, CD33, CD64, CD71, MPO, and HLA-DR, which indicated acute leukemia of the myeloid lineage with a monocytic component. Chromosomal analysis of the BM specimen showed 46,XX,t(11;19)(p15;p12)[26]/46,XX[1] (Fig. 1B). FISH analysis showed normal genotypes for AML1-ETO, PML-RARα, CBFB, and MLL. In the real-time allele-specific PCR assay for FLT3 mutations, a D835Y mutation was detected. Multiplex reverse transcriptase PCR using Hemavision kit (DNA Technology, Aarhus, Denmark) did not detect any other mutations. For further evaluation, we sent the BM samples out for WGS and RNA sequencing (RNA-seq) analysis. The WGS analysis was performed by using the HiSeq X Ten system (Illumina, San Diego, CA, USA), and RNA-seq analysis was performed by using the 100-bp paired-end mode of the TruSeq Rapid PE Cluster kit and the TruSeq Rapid SBS kit (Illumina, San Diego, CA, USA). The WGS analysis revealed the presence of 16 in-frame gene fusions, including a fusion between NUP98 and ZNF91 (Fig. 2A). To clarify these findings, additional FISH analyses using the NUP98 break-apart FISH probe kit (Empire Genomics,

A retrospective analysis of cytogenetic alterations in patients with newly diagnosed multiple myeloma: a single center study in Korea

Background The accurate identification of cytogenetic abnormalities in multiple myeloma (MM) has become more important over recent years for the development of new diagnostic and prognostic markers. In this study, we retrospectively analyzed the cytogenetic aberrations in MM cases as an initial assessment in a single institute. Methods We reviewed the cytogenetic results from 222 patients who were newly diagnosed with MM between January 2000 and December 2015. Chromosomal analysis was performed on cultured bone marrow samples by standard G-banding technique. At least 20 metaphase cells were analyzed for karyotyping. Results Clonal chromosome abnormalities were detected in 45.0% (100/222) of the patients. Among these results, 80 cases (80.0%) had both numerical and structural chromosome abnormalities. Overall hyperdiploidy with structural cytogenetic aberrations was the most common finding (44.0%), followed by hypodiploidy with structural aberrations (28.0%). Amplification of the long arm of chromosome 1 and -13/del(13q) were the most frequent recurrent abnormalities, and were detected in 50 patients (50.0%) and 40 patients (40.0%) with clonal abnormalities, respectively. The most common abnormality involving 14q32 was t(11;14)(q13;q32), which was observed in 19 cases. Conclusion These findings demonstrate that myeloma cells exhibit complex aberrations regardless of ploidy, even from a single center in Korea. Conventional cytogenetic analysis should be included in the initial diagnostic work-up for patients suspected of having MM.