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Min Kyoung Kim,
Cheolwon Suh,
Hyun Sook Chi, Hee Soon Cho,
Young Kyung Bae,
Kyung Hee Lee,
Gyeong-Won Lee,
In-Suk Kim,
Hyeon-Seok Eom,
Sun-Young Kong,
Sung Hwa Bae,
Hun Mo Ryoo,
Im-Hee Shin,
Yeung-Chul Mun,
Hwasoon Chung,
Myung Soo Hyun
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ABSTRACT: We evaluated the impact of functional polymorphisms in the vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor 2 (VEGFR2) genes on the survival of patients with diffuse large B cell lymphoma (DLBCL). Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression-free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA + TA genotypes had significantly better OS (P = 0.002) and PFS (P = 0.004) than those with the TT genotype. The association between significantly better OS and the AA + TA genotypes was observed separately in patients with low (0-2; P = 0.035) and high (3-5; P = 0.043) International Prognostic Index scores. Multivariate analysis showed that, relative to the AA + TA genotypes, the TT genotype was an independent prognostic factor for poor OS (HR, 1.71; 95% CI, 1.21-2.43; P = 0.002) and PFS (HR, 1.57; 1.13-2.17; P = 0.004). Other independent significant predictors of survival in patients with DLBCL were International Prognostic Index score, age > 60 years, lactate dehydrogenase concentration >normal, extranodal disease >1 and presence of B symptoms. The VEGFR2 rs1870377 polymorphism might affect survival in patients with DLBCL, suggesting that angiogenesis might be related to poor survival in these patients.
Cancer Science 11/2011; 103(3):497-503. · 3.33 Impact Factor
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ABSTRACT: Factor XI (FXI) deficiency is a rare autosomal recessive coagulation disorder most commonly found in Ashkenazi and Iraqi Jews, but it is also found in other ethnic groups. It is a trauma or surgery-related bleeding disorder, but spontaneous bleeding is rarely seen. The clinical manifestation of bleeding in FXI deficiency cases is variable and seems to poorly correlate with plasma FXI levels. The molecular pathology of FXI deficiency is mutation in the F11 gene on the chromosome band 4q35. We report a novel mutation of the F11 gene in an 18-year-old asymptomatic Korean woman with mild FXI deficiency. Pre-operative laboratory screen tests for lipoma on her back revealed slightly prolonged activated partial thromboplastin time (45.2 sec; reference range, 23.2-39.4 sec). Her FXI activity (35%) was slightly lower than the normal FXI activity (reference range, 50-150%). Direct sequence analysis of the F11 gene revealed a heterozygous A to G substitution in nucleotide 1517 (c.1517A>G) of exon 13, resulting in the substitution of aspartic acid with glycine in codon 506 (p.Asp506Gly). To the best of our knowledge, the Asp506Gly is a novel missense mutation, and this is the first genetically confirmed case of mild FXI deficiency in Korea.
The Korean Journal of Laboratory Medicine 10/2011; 31(4):290-3. · 0.63 Impact Factor
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ABSTRACT: The objective of this study was to explore whether individual variations in the concentration of growth factors (GFs) influence the biologic effects of platelet-rich plasma (PRP) on human mesenchymal stem cells (HMSCs).
The concentrations of 7 representative GFs in activated PRP (aPRP) were measured using ELISA. The effects of PRP on the proliferation and alkaline phosphatase (ALP) activity of HMSCs were examined using several concentrations of aPRP from 3 donors; the relationships between the GF levels and these biologic effects were then evaluated using 10% aPRP from 5 subgroups derived from 39 total donors. HMSCs were cultured in DMEM with the addition of aPRP for 4 or 12 days; then, DNA content and ALP activity were measured.
The quantity of DNA increased significantly at a 10% concentration of aPRP, but the ALP activity was suppressed at this concentration of aPRP. The GF concentrations varied among donors, and 5 subgroups of characteristic GF release patterns were identified via cluster analysis. DNA levels differed significantly between groups and tended to be higher in groups with higher concentrations of transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factors (PDGFs). DNA quantity was positively correlated with TGF-β1 concentration, and was negatively correlated with donor age. ALP activity was negatively correlated with PDGF-BB concentration.
The varying GF concentrations may result in different biologic effects; thus, individual differences in GF levels should be considered for reliable interpretation of the biologic functions and standardized application of PRP.
The Korean Journal of Laboratory Medicine 07/2011; 31(3):212-8. · 0.63 Impact Factor
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Min Kyoung Kim,
Sung Hwa Bae,
Young Kyung Bae,
Yoon-Seup Kum,
Hun Mo Ryoo, Hee Soon Cho,
Kyung Hee Lee,
Sung Ae Koh,
Ha Young Lee,
So Yeon Yun,
Jun Hyeok Choi,
Myung Soo Hyun
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ABSTRACT: Diffuse large B cell lymphoma (DLBCL) of primary nodal (PN) or primary extranodal (PEN) origin may differ immunophenotypically, in that PEN lymphoma cells may originate from activated rather than germinal center B (GCB) cells. We evaluated the relationship between DLBCL clinicopathological features, including expression of B-cell differentiation markers, and primary tumor site.
Expression of CD10, Bcl-6, Bcl-2, and MUM1 was determined in paraffin-embedded tissues from 123 patients with DLBCL.
Of the 123 patients with DLBCL, 40 (32.5%) had the GCB and 83 (67.5%) had the non-GCB phenotype. Fifty-one patients (42%) showed disease involvement at PEN sites, including 29 with disease in the gastrointestinal (GI) tract (14 in the stomach, 15 in the intestine). Of these 51 patients, 16 (31.4%) were classified with the GCB and 35 (68.5%) with the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes among primary sites. Of the 72 patients with PN DLBCL, 22 (31%) had the GCB and 50 (69%) had the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes between patients with PN and PEN DLBCL. Although lactate dehydrogenase (LDH) concentration > normal, stage >II, and rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) treatment were independent predictors of overall survival (OS), GCB subtype, and presence of PEN disease failed to predict survival upon multivariate analysis.
There was no difference in GCB and non-GCB phenotypes between patients with PN and PEN DLBCLs. Additional studies are needed to further assess molecular differences between the two groups.
Clinical lymphoma, myeloma & leukemia 06/2011; 11(5):403-8.
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ABSTRACT: In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.
The Korean Journal of Laboratory Medicine 12/2010; 30(6):585-90. · 0.63 Impact Factor
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Leukemia & lymphoma 06/2010; 51(6):1144-7. · 2.40 Impact Factor
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ABSTRACT: Partial trisomy 2p is a rare but relatively well-defined syndrome with distinctive clinical features, including marked psychomotor delay, dysmorphic face, and congenital heart disease. The phenotype of trisomy 18p is variable, from normal appearance to moderate mental retardation. Most cases of trisomy 2p and trisomy 18p result from the inheritance of an unbalanced segregant from a balanced parental translocation or due to de novo duplication. Here, we present the first report of a combined partial trisomy 2p and trisomy 18p due to a supernumerary marker chromosome (SMC). The final karyotype of the patient was 47,XX,+der(18)t(2;18)(p23.1;q11.1)[22]/46,XX[8]. The patient had typical dysmorphic features of partial trisomy 2p23-pter syndrome and congenital heart disease. SMCs are remarkably variable in euchromatic DNA content and mosaicism level. The precise identification of the origin and composition of SMCs is essential for genotype-phenotype correlation and genetic counseling.
The Korean Journal of Laboratory Medicine 06/2010; 30(3):312-7. · 0.63 Impact Factor
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ABSTRACT: The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline.
Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed.
The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment.
The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.
Journal of Preventive Medicine and Public Health 08/2009; 42(4):261-6.
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Leukemia research 07/2009; 33(9):e159-61. · 2.36 Impact Factor
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ABSTRACT: Chromosome 1 band p32 (1p32) aberrations are common in T lymphoblastic leukemia/lymphoma (T-ALL/LBL). Two types of 1p32 aberrations include translocations with different partners and submicroscopic interstitial deletion. Both aberrations are known to result in TAL1 gene deregulation. The t(1;5)(p32;q31) is a rare translocation of 1p32 in T-ALL. We now present the second case of t(1;5)(p32;q31) in T-ALL, which was present as a primary cytogenetic abnormality, with a review of the relevant literature. Interestingly, neither the translocation of the TAL1 gene nor aberrant expression of TAL1 protein was detected by fluorescent in situ hybridization (FISH) and by immunohistochemical staining in this case.
The Korean Journal of Laboratory Medicine 07/2009; 29(3):199-203. · 0.63 Impact Factor
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ABSTRACT: Trisomy 19 is frequently encountered in cases of chronic myeloid leukemia (CML) as a secondary abnormality: however, trisomy 19 rarely occurs as a sole chromosomal abnormality and, to date, it has only been reported in 48 hematopoietic malignancies, 1 case of adenocarcinoma and 1 case of astrocytic tumor. Here, we report two additional cases of trisomy 19 as a sole karyotypic aberration in myeloid malignancies. One of these cases involved a 6-month-old male who was diagnosed with acute myeloid leukemia minimally differentiated. His karyotype was 47,XY,+19[20]. He expired 5 days after diagnosis. Another case occurred in an 80-yr-old female who had refractory anemia with excess blasts. Her karyotype was 47,XX,+19[16]/46,XX[4]. Four months later, her peripheral blood smears suggested that the disease had progressed, but she refused further evaluation. Based on a review of the existing literature and the results of this report, trisomy 19 not only as a secondary abnormality but also as a sole karyotypic aberration is strongly associated with myeloid disorder; however, it is not preferentially found in specific FAB subgroups of myelodysplasic syndrome or acute myeloid leukemia.
The Korean Journal of Laboratory Medicine 07/2008; 28(3):174-8. · 0.63 Impact Factor
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ABSTRACT: This study is conducted to determine the effect of different kinds of bone substitutes and collagen on the concentration of platelet-derived growth factor (PDGF) and transforming growth factor beta-1 (TGF beta-1) in platelet-rich plasma (PRP). PRP is treated with thrombin, hydroxyapatite (HA), and thrombin, HA alone, collagen-grafted HA, calcium metaphosphate (CMP), and collagen-grafted CMP. The concentrations of PDGF-AB and TGF beta-1 are measured. After PRP treated with HA and CMP, the concentrations of PDGF and TGF beta-1 are not significantly different from the concentration of them in PRP alone. The concentrations of PDGF in PRP with collagen-grafted HA and collagen-grafted CMP are significantly higher than that of PRP with HA and CMP. The concentrations of PDGF and TGF beta-1 in PRP with collagen-grafted CMP are higher than with collagen-grafted HA. The results of multiple regression analysis show that PDGF increased with the use of collagen and thrombin, and is higher in native whole blood with higher platelet counts. However, PDGF decreased with the use of HA. In conclusion, HA and CMP do not seem to be able to activate platelets by themselves. However, if they had collagen grafted onto them, they could activate platelets and release growth factors.
Journal of Biomaterials Applications 06/2008; 22(6):545-57. · 2.08 Impact Factor
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ABSTRACT: Hemophagocytic syndrome, cytomegalovirus infection and systemic lupus erythematosus (SLE) would each be critical diseases separately. Viral infections, autoimmune diseases or malignancies can complicate the Hemophagocytic syndrome. Cytomegalovirus infection is known to be prevalent in immune compromised hosts, and can exacerbate the symptoms of systemic lupus erythematosus. A 25-year-old man presented with fever and acute pericarditis with the hemophagocytic syndrome, cytomegalovirus infection and systemic lupus erythematosus; all developed concurrently at the onset of illness. With treatment, using ganciclovir and glucocorticoid medication the patient improved. Here we report this rare case and review the medical literature.
Rheumatology International 02/2008; 28(3):271-3. · 1.88 Impact Factor
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ABSTRACT: Waldenstrom's macroglobulinemia is an uncommon low-grade B-cell lymphoproliferative disorder in which monoclonal immunoglobulin M is produced. Neurological symptoms due to hyperviscosity are frequent manifestations of Waldenstrom's macroglobulinemia. However, central nervous system infiltration by plasmacytoid lymphocytes (Bing-Neel syndrome) has only rarely been reported. We report a case of a 51-yr-old woman suffering from Waldenstrom's macroglobulinemia who complained of persistant headache. Brain magnetic resonance imaging revealed an extra-axial soft tissue mass along the left cavernous sinus, left tentorium, right tentorium, and falx cerebri. A stereotactic biopsy of dural tissue from the falx was performed and showed plasmacytoid lymphocyte infiltration. The patient became symptom- free with irradiation of the whole brain followed by chemotherapy with fludarabine.
Journal of Korean Medical Science 01/2008; 22(6):1079-81. · 0.99 Impact Factor
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ABSTRACT: TNF-alpha mediated apoptosis of the hematopoietic cells has been thought to contribute to the ineffective hematopoiesis observed in myelodysplastic syndrome (MDS). The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS. The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS. 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy. At baseline, the patient's median age was 60 yr (range: 18-75 yr). The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1). 11 patients (52%) had at least single lineage response. 3 patients (11%) showed improvement of triple lineage cytopenia. There were no differences in the response rates between the FAB subtypes. The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days). These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.
Journal of Korean Medical Science 03/2006; 21(1):40-5. · 0.99 Impact Factor
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ABSTRACT: A therapy-related myelodysplastic syndrome (t-MDS) during the course of Waldenström's macroglobulinemia (WM) has been observed in rare patients. In most of them, the condition developed after treatment with alkylating agents. We experienced a 65-year-old male patient who was diagnosed as WM. He was treated with intermittent oral chlorambucil for 12 months and three cycles of fludarabine, and complete response was achieved after fludarabine treatment. During routine outpatient follow-up, severe anemia occurred. His bone marrow aspirate showed dysplastic hemopoiesis with ringed sideroblasts and siderocytes, which is consistent with MDS (refractory anemia with ringed sideroblasts). Cytogenetic analysis showed complex chromosomal abnormalities including 5q deletion, 12p deletion and monosomy 18. When decision is made to treat WM with chlorambucil and/or fludarabine, a potential risk for t-MDS or therapy-related acute myeloid leukemia should be considered and a close hematologic monitoring is needed.
Japanese Journal of Clinical Oncology 11/2005; 35(10):622-5. · 1.78 Impact Factor
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ABSTRACT: Non-Hodgkin's lymphomas of the orbit and ocular adnexa (OOA), the majority of which are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue-type (MALT lymphomas), are a rare disorder. The aim of this study was to evaluate the clinical features and treatment outcomes and complications in patients with MALT lymphoma of OOA. Thirty-seven patients with a histologically verified diagnosis of MALT lymphoma of OOA were included in this retrospective, observational case study. There were 22 (59%) men and 15 (41%) women, with a median age of 44 years (range, 21-80 years). The most common presenting complaint was a slowly growing orbital mass. The stages were IA(E) in 74%, IA(EE) (bilateral involvement) in 18%, IIIA(E) in 6%, and IVA(E) in 3%. None of the patients had an elevated value of LHD or beta(2)-microglobulin. Surgical resection alone was attempted as the sole treatment in two patients, but tumor recurred 19 and 24 months after surgery. Radiotherapy, with a median tumor dose of 3,060 cGy, was administered in 29 patients; all of the patients achieved complete remission, and none of them had severe later complications. Combination chemotherapy alone was employed in three patients with stage IIIA(E) or IVA(E). With a median follow-up duration of 21 months, the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 97% and 86%, respectively. Subgroup analysis of the patients with localized disease, who received radiotherapy as an initial treatment modality, revealed that 3-year OS rate and EFS rate were 100% and 93%, respectively. All disease recurrences were documented histologically as MALT lymphoma. In conclusion complete staging evaluation is needed to select an adequate treatment modality. Radiotherapy alone can produce excellent local control and survival in patients with localized MALT lymphoma of OOA. Systemic chemotherapy should be considered in patients with advanced stages or systemic manifestation.
Annals of Hematology 02/2005; 84(1):13-8. · 2.62 Impact Factor
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ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is a disseminated form of thrombotic microangiopathy. Although most cases are held to be idiopathic, its association with malignancy is well recognized and it usually occurs at the terminal stage of cancer. Bone marrow necrosis (BMN) is another rare disorder defined pathologically as the necrosis of myeloid tissue and medullary stroma with preservation of bone. While hematologic malignancy is the most common underlying disease associated with BMN, it can also be caused by solid tumors. Neither TTP nor BMN associated with colon cancer has been reported. We describe here a patient with the rare association of TTP and BMN displayed as the first manifestation of an advanced colon cancer. The anemia and thrombocytopenia responded not to plasma exchange but to the combination chemotherapy. This case indicates that metastatic cancer should be included in the differential diagnosis of TTP and BMN, and that the chemotherapy may improve the detrimental clinical course.
Japanese Journal of Clinical Oncology 09/2004; 34(8):476-80. · 1.78 Impact Factor
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ABSTRACT: The involvement of central nervous system is rare in acute promyelocytic leukemia (APL). We report a APL patient of a 41 yr-old Korean male who presented with fever and petechia. Complete molecular remission was achieved with all-trans retinoic acid (ATRA), idarubicin, and cytarabine. Ten months later, he complained of a mild headache. The results of the physical examination and the complete blood counts were normal. The examination of cerebrospinal fluid showed the presence of promyelocyte. Bone marrow studies showed cytogenetic remission but with molecular relapse. He was treated with intrathecal and systemic chemotherapy.
Journal of Korean Medical Science 05/2004; 19(2):311-4. · 0.99 Impact Factor
