Eun Hae Cho

Imatinib mesylate discontinuation in patients with chronic myeloid leukemia who have received front-line imatinib mesylate therapy and achieved complete molecular response

The aims were to investigate the feasibility of imatinib mesylate (IM) discontinuation in chronic myeloid leukemia patients who were initially treated with IM and achieved complete molecular response (CMR). Fourteen patients were included. Ten were relapsed within 9.5 months after discontinuation of IM. All 7 patients with high Sokal risk were relapsed. The probability of CMR persistence at 1-year was 28.6%. All relapsed patients were still responsive to IM. A high Sokal risk and delayed acquisition of CMR were associated with relapse. IM discontinuation in patients achieved CMR after treatment with front-line IM might be feasible. Further studies are warranted.

FISH-negative cryptic PML–RARA rearrangement detected by long-distance polymerase chain reaction and sequencing analyses: a case study and review of the literature

Although a normal karyotype according to conventional cytogenetic analysis in association with cryptic t(15;17) has been infrequently reported in cases of acute promyelocytic leukemia (APL), a fluorescence in situ hybridization (FISH)-negative cryptic PML-RARA rearrangement is even more rare, with only 12 such APL cases of FISH-negative cryptic PML-RARA rearrangements in the literature. Reported here is an additional clinical APL case with a FISH-negative cryptic PML-RARA rearrangement, confirmed by long-distance DNA polymerase chain reaction method. Discussion includes a relevant literature review of similar cases. DNA-PCR can be a useful tool for the analysis of complex and cryptic rearrangements.

High-resolution melting curve analysis for rapid detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis clinical isolates.

ABSTRACT We evaluated high-resolution melting (HRM) curve analysis as a tool for detecting rifampin (RIF) and isoniazid (INH) resistance in Mycobacterium tuberculosis in an accurate, affordable, and rapid manner. Two hundred seventeen M. tuberculosis clinical isolates of known resistance phenotype were used. Twenty-nine known rpoB mutant DNAs, including rare mutations, were also included. Four pairs of primers were designed: rpoB-F/R (for codons 516 to 539 of rpoB), rpoB-516F/R (for codons 508 to 536 of rpoB), katG-F/R (for the codon 315 region of katG), and inhA-F/R (for the nucleotide substitution of C to T at position −15 of inhA). An HRM curve was generated for each isolate after real-time PCR differentiated the mutant from the wild-type strains. DNA sequencing of the target regions was performed to confirm the results of the HRM curve analysis. All but one of the 73 RIF-resistant (RIF-R) strains and all 124 RIF-susceptible (RIF-S) isolates were correctly identified by HRM curve analysis of rpoB. Twenty-seven of 29 known rpoB mutants were detected. In HRM curve analysis of katG and inhA, 90 INH-R strains that harbored katG or inhA mutations, or both, and all INH-S strains were correctly identified. Ten phenotypically INH-R strains not harboring katG or inhA mutations were not detected. The HRM curve analysis will be a useful method for detection of RIF and INH resistance in M. tuberculosis in a rapid, accurate, simple, and cost-effective manner.

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.

Validation of QF–PCR in a Korean population

Quantitative fluorescence polymerase chain reaction (QF‐PCR) is a rapid and reliable method for screening common aneuploidies, but it is not an accustomed way of testing in Korea. Our objectives were to investigate QF‐PCR as a means for prenatal aneuploidy screening and to evaluate the short tandem repeat (STR) markers in a Korean population.

Genomic breakpoints and clinical features of MLL-TET1 rearrangement in acute leukemias

Recent rapid developments in new technology such as whole genome/exome sequencing have revealed that novel mutations in genes such as DNMT3A , IDH1 , IDH2 and TET2 contribute to the main process of leukemogenesis in patients with normal karyotype acute myeloid leukemia (AML).[1][1] Among these genes

De novo Acute Myeloid Leukemia Associated with t(11;17)(q23;q25) and MLL-SEPT9 Rearrangement in an Elderly Patient: A Case Study and Review of the Literature

a Department of Laboratory Medicine, Armed Forces Capital Hospital, Seongnam , b Department of Laboratory Medicine, School of Medicine, Kyung Hee University, and Departments of c Internal Medicine and d Laboratory Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul , e Department of Laboratory Medicine, Inje University College of Medicine, Busan , and f Greencross Reference Laboratory, Yongin , Korea; g Institute of Pharmaceutical Biology, ZAFES, Diagnostic Center of Acute Leukemia, Goethe University of Frankfurt, Biocenter, Frankfurt/Main , Germany

Mowat–Wilson syndrome detected by using high resolution microarray

Individuals with Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene. This deletion or cytogenetic abnormality has been reported primarily from Europe, Australia and the United States, but not in Korea. Here we report a patient with characteristic facial features of MWS, developmental delay and spasticity. High resolution microarray analysis revealed 0.9 Mb deletion of 2q22.3 involving two genes: ZEB2 and GTDC1. This case shows the important role of high resolution microarray in patients with unexplained psychomotor retardation and/or facial dysmorphism. Knowledge about the most striking clinical signs and implementation of effective molecular tests like microarray could significantly increase the detection rate of new cases of MWS in Korea. This is the first reported case of MWS in Korea.

Acute promyelocytic leukemia with trisomy 8 showing normal PML-RARA FISH signal patterns: diagnostic application of long-distance polymerase chain reaction in molecularly discrepant leukemia cases.

Dear Editor, In the recent published article “FISH-negative cryptic PMLRARA rearrangements detected by long-distance polymerase chain reaction and sequencing analyses: a case study and review of literature,” we have reviewed and listed most of the reported cases of cryptic PML-RARA rearrangements so far [1]. In this study, we report an additional rare case of PML-RARA fluorescence in situ hybridization (FISH)-negative acute promyelocytic leukemia (APL) associated with trisomy 8 and discuss briefly on the relatively high frequency of Korean APL patients showing cryptic PMLRARA rearrangements. This novel case was again analyzed and characterized at molecular level by applying longdistance polymerase chain reaction (LD-PCR). A 23-year-old male was referred to our hospital for further evaluation and treatment of ecchymosis and thrombocytopenia. Complete blood count results were: hemoglobin, 12.0 g/dL; platelet count, 36,000/μL; and white blood cell count, 3,940/μL. Leukemic blasts and promyelocytes accounted for 13% of total leukocytes. Bone marrow

Detection of SET-NUP214 rearrangement using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) in acute leukemias: a case report and literature review on a Korean case series

Dear Editor, We read an interesting article in a recent issue of the Annals of Hematology by Chae et al. entitled “Phenotypic and genetic characterization of adult T-cell acute lymphoblastic leukemia with del (9) (q34); SET-NUP214 rearrangement” [1]. Here, we would like to point out why the number of recent reports on the above gene rearrangement in Korea is increasing and suggest the most appropriate molecular diagnostic method for the detection of the SET-NUP214 rearrangement, by reporting a new case of SET-NUP214 from a T-cell acute lymphoblastic leukemia (T-ALL) patient and through literature review of the ten reported cases, including our new case, that reports on acute leukemias with SET-NUP214 in Korea between the 2-year period of 2010–2011 from the literature [1–4]. A 43-year-old Korean woman was examined in the outpatient clinic with fever and skin rash lasting from 50 days ago. She received uterine leiomyomectomy a year ago and had her breast mass monitored periodically. A chest X-ray revealed bilateral mediastinal widening, suggesting huge mediastinal mass or lymphadenopathy and abdominal ultrasonography showed splenomegaly. An initial complete blood count showed a hemoglobin level of 8.8 g/dL, a platelet count of 114×10/L, and a white blood cell count of 60.6×10/L with 85% blasts, 2% neutrophils, and 13% lymphocytes (Fig. 1a). Bone marrow study showed a hypercellularity with markedly increased leukemic blasts (91%, Fig. 1a). The karyotype of the bone marrow cells was 46,XX,dup(1)(p22p36.1) in 16 out of 20 metaphase cells analyzed (Fig. 1b). According to immunophenotyping, blasts were positive for CD3 (84%), CD5 (78%), CD7 (99%), CD13 (43%), CD33 (48%), and CD34 (80%). However, these cells did not express CD10, CD19, CD20, cCD22, CD14, HLA-DR, and myeloperoxidase. Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using bone marrow specimen was performed with HemaVision kit (HemaVision; DNA technology, Aarhus, Denmark) and revealed the presence of SET-NUP214 fusion transcript measuring 393 bp (Fig. 1c). Eun Young Lee and Tae Sung Park equally contributed to this study as first authors. E. Y. Lee : S.-J. Park : J. R. Choi : J.-H. Yoo (*) Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea e-mail: jhyoo92@nhimc.or.kr