BACKGROUND: CpG islands' methylation of p15 promoter region is associated with inactivation of the p15 gene, which negatively regulates the cell cycle. We investigated the prevalence and prog-nostic significance of p15 gene methylation in AML and ALL patients, and sequentially analyzed p15 methylation during the follow-up. METHODS: This study included 52 and 25 bone marrow aspirates from 33 AML and 22 ALL patients, respectively; p15 methylation was analyzed by methylation specific PCR. RESULTS: The methylation of the p15 gene was observed in 57% of newly diagnosed AML, 70% of relapsed AML, and 23% of newly diagnosed ALL patients. Moreover, p15 methylation was found in 65% of AML and 33% of ALL patients with a normal karyotype. No association was found between p15 methylation status and prognostic factors or clinical outcomes; however, p15 methylation status correlated well with the clinical and pathologic features of disease status during the follow-up. CONCLUSIONS: The methylation of the p15 gene may be of use as a marker for disease monitoring of acute myelogeneous leukemia, especially in patients with a normal karyotype, although p15 methy-lation doesn't seem to be associated with prognosis.
Bone Marrow ; Cell Cycle ; Follow-Up Studies ; Humans ; Karyotype ; Leukemia* ; Methylation* ; Polymerase Chain Reaction ; Prevalence* ; Prognosis ; Promoter Regions, Genetic

BACKGROUND: It is important to distinguish between the constitutional and acquired chromosomal abnormality in bone marrow of the patients with the hematologic malignancies, since the constitutional chromosomal abnormality will be continuously observed, even though in remission status of the disease. In this study, we investigated the incidence and types of constitutional chromosomal abnormalities in patients with the hematologic malignancies. METHODS: This study included 396 patients with benign hematologic disorders and 634 with hematologic malignancies. The cytogenetic analysis of bone marrow aspirates were performed by direct or/and short term culture (24-48 hours). The constitutional chromosomal abnormality was confirmed by phytohemagglutinin-stimulated 72 hour culture with peripheral blood lymphocytes. RESULTS: The incidence of constitutional chromosomal abnormalities was 2.8% in patients with benign hematologic disorders and 2.4% in patients with hematologic malignancies. Among the patients with constitutional chromosomal abnormalities and hematologic malignancies, 12 were males and 3 females. Eleven patients had an age greater than 20 years. One patient had trisomy 21, 1 reciprocal translocation, 1 robertsonian translocation, 3 sex chromosome aneuploidy and 9 inv(9). Two patients showed both constitutional and acquired chromosomal abnormalities on the same chromosome. The constitutional chromosomal abnormality was continuously observed in remission status of hematologic malignancies. CONCLUSIONS: The incidence of the constitutional chromosomal abnormalities was low in patients with hematologic malignancies, but the chromosome study with peripheral blood or skin fibroblasts may be necessary for determining accurate cytogenetic response during follow up.
Aneuploidy ; Bone Marrow ; Chromosome Aberrations* ; Cytogenetic Analysis ; Cytogenetics ; Down Syndrome ; Female ; Fibroblasts ; Hematologic Neoplasms* ; Humans ; Incidence* ; Lymphocytes ; Male ; Sex Chromosomes ; Skin

ider(9)(q10)t(9;22)(q34;q11.2) is an isochromosome for the long arm of a derivative chromosome 9 generated by a t(9;22), resulting from the deletion of the short arm of chromosome 9. It is known to be rarely observed in acute lymphoblastic leukemia (ALL) or lymphoblastic crisis transformed from chronic myelogenous leukemia. We herein describe a 26-year-old female patient with precursor B-cell ALL, cytogenetically characterized by ider(9)(q10)t(9;22). Fluorescence in situ hybridization analysis showed two ABL-BCR fusion signals on the derivative chromosome 9 and one BCR-ABL fusion signal on the derivative chromosome 22. Although a t(9;22) and a deletion of the short arm of chromosome 9 are known to be associated with a poor prognostic factor in acute lymphoblastic leukemia, a larger study is needed to determine the prognosis of ider(9)(q10)t(9;22) cases.
Adult ; Arm ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Female ; Fluorescence ; Humans ; In Situ Hybridization ; Isochromosomes ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, B-Lymphoid ; Prognosis

PURPOSE: The purpose of this study was to investigate the goals, methods and opinions of medical students on self-directed learning (SDL) and to compare the self-assessments with faculty-evaluations. METHODS: The study group included 90 medical students doing their clerkship in the department of Laboratory Medicine, Mokdong Hospital, Ewha Womans University, School of Medicine, Seoul, Korea, from August 2005 to October 2006. Students were asked to review cases, formulate learning goals, implement appropriate learning strategies and present learning outcomes. Students' opinions on SDL were collected. Their self-assessments were compared with the faculty evaluation scores using the same checklist. Three groups were defined according to the faculty scores: scores >12, high; scores 10~12, middle; scores <9, low. RESULTS: SDL was helpful in increasing confidence in students' own learning abilities and in raising interest in the patient-doctor relationship. Some students had difficulty formulating learning goals on their own. The mean of the self-assessments was significantly higher than that of faculty mean (11.8+/-2.1 vs. 10.9+/-2.3, p=.005). Rater agreement by items was approximately 30%. There was significant interaction between raters and group. Among the 'high' group, 55% under-rated their scores to middle or low levels, whereas 66% of the 'low' group rated themselves higher to high or middle levels. Spearman's correlation coefficient between faculty's and student's scores was r=.219 (p=.038) and 4.4% of the faculty evaluations was predicted by the self-assessment scores. CONCLUSION: These results suggest that SDL is an effective learning tool during clerkship. Since students' scores did not correlate with those of the faculty's, students need to develop appropriate self-assessment skills.
Checklist ; Female ; Humans ; Korea ; Learning ; Self-Assessment ; Students, Medical

BACKGROUND: The origin of hematologic malignancies has been known to be monoclonal. In most cases, the same or obviously related chromosomal abnormliaties are found and cytogenetically unrelated clones are uncommon. We evaluated the prevalence and clinical significance of patients with cytogenetically unrelated clones in hematologic malignancies. METHODS: Included in the study were 324 patients who had been diagnosed with the following hematologic malignancies at Ewha Womans University, Mokdong Hospital: AML (93 cases), MDS (27), CML (51), myeloproliferative disorder (38), acute biphenotypic leukemia (8), ALL (44), CLL (9), multiple myeloma (MM, 40), and Non-Hodgkin's lymphoma with bone marrow involvement (14). RESULTS: The overall prevalence of hematologic malignancies with cytogenetically unrelated clones at diagnosis was 0.9% (3/324). Of AML patients, 1.1% (1/93) had unrelated clones, CLL 11.1% (1/9), and MM 2.5% (1/40). The other hematologic malignancies did not show cytogenetically unrelated clones. The AML patient had add(11)(q23)/add(1)(p36.3); the CLL patient had +12/ del(13)(q22); and the MM patient had +der(1)t(1;13)(p12;q12), -13/-X, +5, +7, -8, -12, -13, add(14) (q32), +15, -16, +19, -20, -22, -22. We also detected an unrelated clone of trisomy 8 in Philadelphia chromosome negative cells from a CML patient who was treated with imatinib mesylate. CONCLUSIONS: Hematologic malignancies with cytogenetically unrelated clones are uncommon. This report highlights the importance of the conventional chromosomal analysis in that an unrelated clone in philadelphia chromosome negative cells may be detected in a CML case.
Bone Marrow ; Clone Cells* ; Diagnosis ; Female ; Hematologic Neoplasms* ; Humans ; Leukemia, Biphenotypic, Acute ; Lymphoma, Non-Hodgkin ; Mesylates ; Multiple Myeloma ; Myeloproliferative Disorders ; Philadelphia Chromosome ; Prevalence ; Trisomy ; Imatinib Mesylate

Chemotherapy agents can induce chromosomal instability, including a variety of chromatid or chromosomal aberrations. However, only limited data is available on the effect of chemotherapy on the kinetics of chromosomal instability in peripheral blood lymphocytes. Here, we report the case of an ovarian cancer patient who showed chromosomal instability in peripheral blood lymphocytes while undergoing chemotherapy. Karyotypic analysis of peripheral blood 1 day after administration of cisplatin and etoposide showed chromosomal or chromatid aberrations, including gaps, breaks, and fragmentation. Chromosome study after completion of the first chemotherapy cycle showed normal karyotype. This finding suggests that chemotherapeutic agents can induce transient chromosomal instability in peripheral blood lymphocytes.
Chromatids ; Chromosomal Instability ; Chromosome Aberrations ; Cisplatin ; Etoposide ; Humans ; Karyotype ; Kinetics ; Lymphocytes ; Ovarian Neoplasms

BACKGROUND: Because of a lack of substances for platelet (PLT) metabolism and preservation, normal saline (NS) washed PLTs can only be stored for short lengths of time. However, the use of platelet additive solutions (PAS) could help solve this problem. In this study, the in vitro quality of NS washed platelets (wPLTs) stored in two types of PAS were compared with those of wPLTs stored in NS. METHODS: Five units of NS washed apheresis platelets were pooled aseptically and separated into five aliquots for storage in NS only as well as T-PAS+ (Terumo BCT, Lakewood, CO, USA) and CompoSol PS (Fenwal, Lake Zurich, IL, USA) with or without 15 mM glucose. The parameters of wPLTs quality were assessed up to 48 hrs after washing and the whole experiment was repeated 10 times independently. RESULTS: wPLTs in two kinds of PAS had better quality than wPLTs in NS, and wPLTs in T-PAS+ showed better quality than those in CompoSol PS. PAS-stored wPLTs with added glucose maintained stable CD62P and Annexin V expression during storage, but exhibited increased lactate accumulation. Evaluation of in vitro quality revealed that all wPLTs had a rating of 4 immediately after washing. However, only T-PAS+-stored wPLTs with glucose maintained a rating of 4 up to 48 hrs of post-washing. CONCLUSION: Using PAS storage for wPLTs may be beneficial compared to NS. The results presented herein suggest that T-PAS+ containing glucose has the potential to extend storage time by up to 48-hours.
Annexin A5 ; Blood Component Removal ; Blood Platelets* ; Blood Preservation ; Glucose ; In Vitro Techniques ; Lactic Acid ; Lakes ; Metabolism

BACKGROUND: Loss of sex chromosomes in bone marrow is observed both in elderly persons as an aging phenomenon and in patients with hematologic malignancies. The purpose of this study was to evaluate the incidence and clinical significance of sex chromosome losses in patients with hematologic diseases, comparing the characteristics between patients with sole and secondary sex chromosome losses in conjunction with other chromosomal abnormalities. METHODS: Study group included 868 patients with hematologic diseases between June 1998 and May 2006. The cells of bone marrow aspirates were processed using unstimulated culture methods such as direct, 24-hr and/or 48-hr culture. Sex chromosome losses were included in the karyotype, when X or Y chromosome loss is observed in more than 2 metaphase cells. RESULTS: The sex chromosome losses in bone marrow were found in 5.1% of the patients and 1.8% showed sex chromosome losses as a sole chromosomal abnormality. According to the disease categories, the incidences of sex chromosome losses were as follows: acute myelogenous leukemia (AML), 9.5%; acute lymphoblastic leukemia, 0%; myelodysplastic syndrome, 6.0%; chronic myelogenous leukemia 3.6%; myeloproliferative disorders, 1.3%; multiple myeloma (MM), 13.0%; chronic lymphocytic leukemia, 0%; malignant lymphoma, 3.8%; and benign hematologic diseases 2.2%. The patients with sex chromosome losses as a sole chromosomal abnormality were all male and median age was higher than that of patients with sex chromosome losses as a secondary abnormality (64 vs. 58 yr, P=0.02). The proportion of metaphase cells with sex chromosome losses was significantly lower in patients with sex chromosome losses as a sole chromosomal abnormality (40% vs. 100%, P<0.0001). The changes of sex chromosome loss were correlated with the disease status of AML and MM. CONCLUSIONS: These results suggest that secondary sex chromosome losses in conjunction with other chromosomal abnormalities seem to be one of the clonal abnormalities, whereas sex chromosome losses as a sole change seem to be an aging phenomenon, but further studies are needed.
Adult ; Aged ; Bone Marrow Cells/*cytology ; *Chromosomes, Human, X ; *Chromosomes, Human, Y ; Female ; Hematologic Diseases/*diagnosis/*genetics ; Humans ; Male ; Middle Aged ; *Sex Chromosome Aberrations

BACKGROUND: The serologic tests for syphilis infection have been performed manually, but the procedures are time-consuming and interpretations may be subjective. Recently, automated assays were developed for rapid and efficient testing for syphilis infection. In this study, we evaluated the performances of IMMUNOTICLES Auto3 RPR and Auto3TP (A&T Corporation, Japan) using latex agglutination turbidimetry method. METHODS: Using 236 serum samples referred for syphilis at Ewha Womans University, Mokdong Hospital, between March 2004 and April 2007, we evaluated precision, linearity, detection limit and compared with the results of manual serologic tests, RPR (RPR card test, ASAN Pharmaceutical, Korea) and TPHA (ASAN-TPHA, ASAN Pharmaceutical). RESULTS: The within-run and between day precisions of Auto3RPR and Auto3TP were from 2.1% to 4.8%. The linearity was good up to 5.0 RU for Auto3RPR and to 250 TU for Auto3TP. Agreement of Auto3RPR with RPR was 65.7% (155/236) and 32.6% of patients (77/236) were RPR positive and Auto3RPR negative. RPR titers were less than 1:8 in 99% of these discrepant samples (76/77) and 65% (50/77) were latent infection and the others were false positive (32%, 27/77). Agreement of Auto3TP with TPHA was 97.1%. CONCLUSIONS: IMMUNOTICLES Auto3RPR and Auto3TP may be useful for rapid and efficient testing for syphilis. However, discrepant results were present in patients with low titer RPR positivity and method of reporting shoud be considered in individual clinical situation. In addition, linear range was not wide and further study is needed for reporting of quantitative results.
Agglutination ; Automation ; Chungcheongnam-do ; Female ; Humans ; Latex ; Limit of Detection ; Nephelometry and Turbidimetry ; Serologic Tests ; Syphilis*

Early diagnosis of acute promyelocytic leukemia (APL) depends primarily on morphological recognition before the presence of t(15;17) or PML-RAR gene rearrangement is confirmed. But the diagnosis is difficult to be made, if typical APL morphologic features are not found. Here, we describe a 32- year old man who had been diagnosed as APL. He relapsed with AML M1 like phenotype, lacking the typical features of APL. At relapse, t(15;17) and PML-RAR alpha gene rearrangement were detected. After 14 days of chemotherapy and all-trans retinoic acid, the phenotype changed from the AML M1 like features to the typical hypergranular APL. Awareness of atypical morphologic subtypes found in APL is important. And identification of t(15;17) or PML/RAR alpha rearrangement will be helpful in diagnosis of atypical APL.
Diagnosis ; Drug Therapy ; Early Diagnosis ; Gene Rearrangement ; Leukemia, Promyelocytic, Acute* ; Phenotype ; Recurrence* ; Tretinoin