PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-18 (18)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
author:("koos, Hoon")
1.  Improved Therapeutic Effect against Leukemia by a Combination of the Histone Methyltransferase Inhibitor Chaetocin and the Histone Deacetylase Inhibitor Trichostatin A 
Journal of Korean Medical Science  2013;28(2):237-246.
SUV39H1 is a histone 3 lysine 9 (H3K9)-specific methyltransferase that is important for heterochromatin formation and the regulation of gene expression. Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells. Histone deacetylase (HDAC) inhibitors inhibit deacetylases and accumulate high levels of acetylation lead to cell cycle arrest and apoptosis. In this study, we demonstrated that treatment with chaetocin enhanced apoptosis in human leukemia HL60, KG1, Kasumi, K562, and THP1 cells. In addition, chaetocin induced the expression of cyclin-dependent kinase inhibitor 2B (p15), E-cadherin (CDH1) and frizzled family receptor 9 (FZD9) through depletion of SUV39H1 and reduced H3K9 methylation in their promoters. Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes. Furthermore, this combined treatment significantly increased loss of SUV39H1 and reduced histone H3K9 trimethylation responses accompanied by increased acetylation. Importantly, co-treatment with chaetocin and TSA produced potent antileukemic effects in leukemia cells derived from patients. These in vitro findings suggest that combination therapy with SUV39H1 and HDAC inhibitors may be of potential value in the treatment of leukemia.
doi:10.3346/jkms.2013.28.2.237
PMCID: PMC3565135  PMID: 23400519
Histone Methyltransferase; Histone Deacetylase; Tumor Suppressor Genes; Leukemia
2.  KDM3B Is the H3K9 Demethylase Involved in Transcriptional Activation of lmo2 in Leukemia 
Molecular and Cellular Biology  2012;32(14):2917-2933.
Histone lysine methylation and demethylation are considered critical steps in transcriptional regulation. In this report, we performed chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis to examine the genome-wide occupancy of H3K9-me2 during all-trans-retinoic acid (ATRA)-induced differentiation of HL-60 promyelocytic leukemia cells. Using this approach, we found that KDM3B, which contains a JmjC domain, was downregulated during differentiation through the recruitment of a corepressor complex. Furthermore, KDM3B displayed histone H3K9-me1/2 demethylase activity and induced leukemogenic oncogene lmo2 expression via a synergistic interaction with CBP. Here, we found that KDM3B repressed leukemia cell differentiation and was upregulated in blood cells from acute lymphoblastic leukemia (ALL)-type leukemia patients. The combined results of this study provide evidence that the H3K9-me1/2 demethylase KDM3B might play a role in leukemogenesis via activation of lmo2 through interdependent actions with the histone acetyltransferase (HAT) complex containing CBP.
doi:10.1128/MCB.00133-12
PMCID: PMC3416203  PMID: 22615488
3.  Implication of Early Lymphocyte Recovery after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Leukemia 
Yonsei Medical Journal  2012;54(1):62-70.
Purpose
The repopulating lymphocytes after allogeneic hematopoietic stem cell transplantation have an important role not only on the prevention of serious infections in the early transplantation period, but also on the killing of residual leukemic cells by graft-versus-leukemia effect. The aim of this study was to analyze the impact of lymphocyte recovery after allogeneic stem cell transplantation in children with hematologic malignancies.
Materials and Methods
We evaluated 69 children transplanted for acute lymphoblastic leukemia (ALL) (n=34), acute myeloid leukemia (AML) (n=26), chronic leukemia (n=7) and juvenile myelomonocytic leukemia (n=2) between 1996 and 2008 at the Chonnam National University Hospital, Korea. The patients were grouped based on absolute lymphocyte counts (ALC) <500/µL or ≥500/µL at D+21 and D+30 after transplant.
Results
Patients with a High ALC at D+21 and D+30 had a faster neutrophil and platelet engraftment. The High at D+30 group had a better 5 year overall survival (71% vs. 53%, p=0.043) and event-free survival (72% vs. 53%, p=0.065) than the Low at D+30 group. The incidence of grade II-IV acute and chronic graft-versus-host disease (GVHD), and relapse rate did not differ by the ALC counts. However, the Low at D+30 group had a significantly increased risk for transplant-related mortality (p=0.019). The univariate analysis showed that the factors associated with decreased survival were a Low ALC at D+30, patients with high risk ALL, and grade II-IV aGVHD in patients with ALL and AML.
Conclusion
Early posttransplant serial lymphocyte measurement would be a simple but useful method for predicting transplant outcomes.
doi:10.3349/ymj.2013.54.1.62
PMCID: PMC3521273  PMID: 23225800
Absolute lymphocyte count; allogeneic stem cell transplantation; children; leukemia
4.  Clinical and hematologic manifestations in patients with Diamond Blackfan anemia in Korea 
The Korean Journal of Hematology  2012;47(2):131-135.
Background
Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years.
Methods
The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study.
Results
The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm3. The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%).
Conclusion
The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.
doi:10.5045/kjh.2012.47.2.131
PMCID: PMC3389062  PMID: 22783360
Diamond Blackfan anemia; Anemia; Congenital defects
5.  Hematopoietic Stem Cell Transplantation in Children with Leukemia: A Single Institution Experience with Respect to Donors 
Journal of Korean Medical Science  2011;26(12):1548-1555.
Aim of this study was to compare the outcomes of transplantation by donor source and to help select the best alternative donor in children with leukemia. Donor sources included matched related donor (MRD, n = 35), allele-matched unrelated donor (M-UD, n = 10) or -mismatched (MM)-UD (n = 13) or unrelated umbilical cord blood (UCB, n = 11). UCB group had a significantly higher incidence of grade II-IV acute graft versus host disease (MRD, 11.8%; M-UD, 30.0%; MM-UD, 15.4%, UCB, 54.4%, P = 0.004) but there was no difference in incidence of chronic graft versus host disease between 4 groups. The 5-yr leukemia-free survival (LFS) was 76.7%, 60.0%, 69.2%, and 45.5%, respectively (P = 0.128). MRD group showed higher LFS rate than UCB group (P = 0.022). However, LFS of M-UD and MM-UD together (65.2%) was not different from that of MRD group (76.7%, P = 0.325), or from that of UCB (45.5%, P = 0.190). The relapse incidence at 5 yr was 17.1%, 20.0%, 15.4%, and 0%, respectively (P = 0.460). The 100-day treatment-related mortality was 2.9%, 20.0%, 7.7%, and 36.4%, respectively (P = 0.011). Despite the limitations of small number of patients, unrelated donor transplants including even allele-mismatched ones, seem to be as effective in children with leukemia lacking suitable relative donors. Also, UCB transplant may serve as another possible option in urgent transplants.
doi:10.3346/jkms.2011.26.12.1548
PMCID: PMC3230013  PMID: 22147990
Allogeneic Hematopoietic Stem Cell Transplantation; Leukemia; Unrelated Donor; Umbilical Cord Blood
6.  Spectra of Chromosomal Aberrations in 325 Leukemia Patients and Implications for the Development of New Molecular Detection Systems 
Journal of Korean Medical Science  2011;26(7):886-892.
This study investigated the spectrum of chromosomal abnormalities in 325 leukemia patients and developed optimal profiles of leukemic fusion genes for multiplex RT-PCR. We prospectively analyzed blood and bone marrow specimens of patients with acute leukemia. Twenty types of chromosomal abnormalities were detected in 42% from all patients by commercially available multiplex RT-PCR for detecting 28 fusion genes and in 35% by cytogenetic analysis including FISH analysis. The most common cytogenetic aberrations in acute myeloid leukemia patients was PML/PARA, followed by AML1/MGT8 and MLL1, and in acute lymphoid leukemia patients was BCR/ABL, followed by TEL/AML1 and MLL1 gene rearrangement. Among the negative results for multiplex RT-PCR, clinically significant t(3;3)(q21;q26.2), t(8;14)(q24;q32) and i(17)(q10) were detected by conventional cytogenetics. The spectrum and frequency of chromosomal abnormalities in our leukemia patients are differed from previous studies, and may offer optimal profiles of leukemic fusion genes for the development of new molecular detection systems.
doi:10.3346/jkms.2011.26.7.886
PMCID: PMC3124718  PMID: 21738341
Leukemia; Chromosomal Abnormalities; Molecular Detection System
7.  Selective embolization of the internal iliac arteries for the treatment of intractable hemorrhage in children with malignancies 
Korean Journal of Pediatrics  2011;54(4):169-175.
Purpose
Acute internal hemorrhage is an occasionally life-threatening complication in pediatric cancer patients. Many therapeutic approaches have been used to control bleeding with various degrees of success. In this study, we evaluated the efficacy of selective internal iliac artery embolization for controlling acute intractable bleeding in children with malignancies.
Methods
We retrospectively evaluated the cases of 6 children with various malignancies (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the internal iliac artery at the Chonnam National University Hwasun Hospital between January 2004 and December 2009. SAE was performed by an interventional radiologist using Gelfoam® and/or Tornado® coils.
Results
The patients were 5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the time of SAE. SAE was performed once in 4 patients and twice in 2, and the procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%) showed improvement after SAE without complications.
Conclusion
SAE may be a safe and effective procedure for controlling acute intractable hemorrhage in pediatric malignancy patients. This procedure may obviate the need for surgery, which carries an attendant risk of morbidity and mortality in cancer patients with critical conditions.
doi:10.3345/kjp.2011.54.4.169
PMCID: PMC3127151  PMID: 21738551
Therapeutic embolization; Pediatric patient; Neoplasms
8.  Differential Gene Expression Analysis in K562 Human Leukemia Cell Line Treated with Benzene 
Toxicological Research  2011;27(1):43-48.
Even though exposure to benzene has been linked to a variety of cancers including leukemia, the detailed molecular mechanisms relevant to benzene-induced carcinogenesis remain to be clearly elucidated. In this study, we evaluated the effects of benzene on differential gene expression in a leukemia cell line. The K562 leukemia cell line used in this study was cultured for 3 h with 10 mM benzene and RNA was extracted. To analyze the gene expression profiles, a 41,000 human whole genome chip was employed for cDNA microarray analysis. We initially identified 6,562 genes whose expression was altered by benzene treatment. Among these, 3,395 genes were upregulated and 3,167 genes were downregulated by more than 2-fold, respectively. The results of functional classification showed that the identified genes were involved in biological pathways including transcription, cell proliferation, the cell cycle, and apoptosis. These gene expression profiles should provide us with further insights into the molecular mechanisms underlying benzene-induced carcinogenesis, including leukemia.
doi:10.5487/TR.2011.27.1.043
PMCID: PMC3834516  PMID: 24278550
Microarray; Benzene; Cell proliferation; Gene expression; Leukemia
9.  Perivascular epithelioid cell tumor (PEComa) of the ascending colon: the implication of IFN-α2b treatment 
Korean Journal of Pediatrics  2010;53(11):975-978.
A 7-year-old boy presented with hematochezia and abdominal pain. A 3.7-cm-sized mass was identified in the ascending colon by abdominal computed tomography and colonoscopy. The patient underwent surgical resection. Pathological examination revealed a low-grade perivascular epithelioid cell tumor (PEComa). PEComa in the colon is very rare. Only a few cases have been reported so far. An effective treatment method for this rare tumor has not been established yet. The patient received adjuvant interferon-α immunotherapy for 1 year. He has been tumor-free for 26 months since the initial diagnosis. This report is the first documented case of the use of interferon-α for pediatric PEComa of the colon.
doi:10.3345/kjp.2010.53.11.975
PMCID: PMC3012279  PMID: 21218021
Perivascular epithelioid cell tumor; PEComa; Colon; Interferon-alpha
10.  Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through histone methylation balance 
Nucleic Acids Research  2010;38(19):6389-6403.
The dynamic exchange of histone lysine methylation status by histone methyltransferases and demethylases has been previously implicated as an important factor in chromatin structure and transcriptional regulation. Using immunoaffinity TAP analysis, we purified the WHISTLE-interacting protein complexes, which include the heat shock protein HSP90α and the jumonji C-domain harboring the histone demethylase JMJD1C. In this study, we demonstrate that JMJD1C specifically demethylates histone H3K9 mono- and di-methylation, and mediates transcriptional activation. We also provide evidence suggesting that both WHISTLE and JMJD1C performs functions in the development of mouse testes by regulating the expression of the steroidogenesis marker, p450c17, via SF-1-mediated transcription. Furthermore, we demonstrate that WHISTLE is recruited to the p450c17 promoter via SF-1 and represses the transcription of prepubertal stages of steroidogenesis, after which JMJD1C replaces WHISTLE and activates the expression of target genes via SF-1-mediated interactions. Our results demonstrate that the histone methylation balance mediated by HMTase WHISTLE and demethylase JMJD1C perform a transcriptional regulatory function in mouse testis development.
doi:10.1093/nar/gkq491
PMCID: PMC2965226  PMID: 20530532
11.  Efficacy of Tandem High-Dose Chemotherapy and Autologous Stem Cell Rescue in Patients Over 1 Year of Age with Stage 4 Neuroblastoma: The Korean Society of Pediatric Hematology-Oncology Experience Over 6 Years (2000-2005) 
Journal of Korean Medical Science  2010;25(5):691-697.
The efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was investigated in patients with high-risk neuroblastoma. Patients over 1 yr of age who were newly diagnosed with stage 4 neuroblastoma from January 2000 to December 2005 were enrolled in The Korean Society of Pediatric Hematology-Oncology registry. All patients who were assigned to receive HDCT/ASCR at diagnosis were retrospectively analyzed to investigate the efficacy of single or tandem HDCT/ASCR. Seventy and 71 patients were assigned to receive single or tandem HDCT/ASCR at diagnosis. Fifty-seven and 59 patients in the single or tandem HDCT group underwent single or tandem HDCT/ASCR as scheduled. Twenty-four and 38 patients in the single or tandem HDCT group remained event free with a median follow-up of 56 (24-88) months. When the survival rate was analyzed according to intent-to-treat at diagnosis, the probability of the 5-yr event-free survival±95% confidence intervals was higher in the tandem HDCT group than in the single HDCT group (51.2±12.4% vs. 31.3±11.5%, P=0.030). The results of the present study demonstrate that the tandem HDCT/ASCR strategy is significantly better than the single HDCT/ASCR strategy for improved survival in the treatment of high-risk neuroblastoma patients.
doi:10.3346/jkms.2010.25.5.691
PMCID: PMC2858826  PMID: 20436703
Neuroblastoma; High-dose Chemotherapy; Transplantation, Autologous
12.  Efficacy and safety of deferiprone (Ferriprox), an oral iron-chelating agent, in pediatric patients 
Background
Iron overload is a predictable and life-threatening complication in patients dependent on the regular transfusion of RBCs. The aims of this study were to investigate the efficacy and safety of deferiprone in a variety of pediatric hematologic and/or oncologic patients with a high iron overload.
Methods
Seventeen patients (age: 1.1-20.4 years; median: 10.6 years) from 7 hospitals who were treated with deferiprone from 2006 to 2009 were enrolled in this study. Medical records of enrolled patients were reviewed retrospectively.
Results
Serum ferritin levels were 4,677.8±1,130.9 µg/L at baseline compared to 3,363.9±1,149.7 µg/L at the end of deferiprone treatment (P=0.033). Only 1 patient developed neutropenia as a complication.
Conclusion
Deferiprone treatment is relatively safe for pediatric patients suffering from various hematologic and oncologic diseases that require RBC transfusions as part of treatment. However, the potential development of critical complications such as agranulocytosis and/or neutropenia remains a concern.
doi:10.5045/kjh.2010.45.1.58
PMCID: PMC2983007  PMID: 21120164
Deferiprone; Iron overload; Transfusion; Neutropenia
13.  Idarubicin Plus Behenoyl Cytarabine and 6-thioguanine Compares Favorably with Idarubicin Plus Cytarabine-based Regimen for Children with Previously Untreated Acute Myeloid Leukemia: 10-Year Retrospective, Multicenter Study in Korea 
We investigated the outcome of idarubicin plus N4-behenoyl-1-β-D-arabinofuranosyl cytosine (BHAC)-based chemotherapy (BHAC group, n=149) compared to idarubicin plus cytarabine-based chemotherapy (cytarabine group, n=191) for childhood acute myeloid leukemia (AML). Between January 1996 and December 2005, 340 children with AML from 5 university hospitals in Korea received the BHAC-based or cytarabine-based chemotherapy, with or without hematopoietic stem cell transplantation. After induction therapy, 264 (77.6%) of 340 children achieved a complete remission (CR) and 43 (12%) achieved a partial remission (PR). The CR rate in the BHAC group was higher than in the cytarabine group (85.2% vs. 71.7%, P=0.004). However, the overall response rate (CR+PR) was not different between the two groups (93.3% vs. 87.9%, P=0.139). The 5-yr estimates of overall survival (OS) of children in the two groups were similar (54.9% for the BHAC group vs. 52.4% for the cytarabine group, P=0.281). Although the results were analyzed according to the treatment type and cytogenetic risk, the OS showed no significant difference between the BHAC group and the cytarabine group. In the present study, the clinical outcomes of the BHAC-based chemotherapy, consisting of BHAC, idarubicin, and 6-TG, are comparable to that of the cytarabine-based chemotherapy for childhood AML.
doi:10.3346/jkms.2010.25.1.9
PMCID: PMC2800026  PMID: 20052341
Leukemia, Myeloid, Acute; Enocitabine; Childhood
14.  Multiple Myeloma-Related WHSC1/MMSET Isoform RE-IIBP Is a Histone Methyltransferase with Transcriptional Repression Activity▿  
Molecular and Cellular Biology  2008;28(6):2023-2034.
Histone methylation is crucial for transcriptional regulation and chromatin remodeling. It has been suggested that the SET domain containing protein RE-IIBP (interleukin-5 [IL-5] response element II binding protein) may perform a function in the carcinogenesis of certain tumor types, including myeloma. However, the pathogenic role of RE-IIBP in these diseases remains to be clearly elucidated. In this study, we have conducted an investigation into the relationship between the histone-methylating activity of RE-IIBP and transcriptional regulation. Here, we report that RE-IIBP is up-regulated in the blood cells of leukemia patients, and we characterized the histone H3 lysine 27 (H3-K27) methyltransferase activity of RE-IIBP. Point mutant analysis revealed that SET domain cysteine 483 and arginine 477 are critical residues for the histone methyltransferase (HMTase) activity of RE-IIBP. RE-IIBP also represses basal transcription via histone deacetylase (HDAC) recruitment, which may be mediated by H3-K27 methylation. In the chromatin immunoprecipitation assays, we showed that RE-IIBP overexpression induces histone H3-K27 methylation, HDAC recruitment, and histone H3 hypoacetylation on the IL-5 promoter and represses expression. Conversely, short hairpin RNA-mediated knockdown of RE-IIBP reduces histone H3-K27 methylation and HDAC occupancy around the IL-5 promoter. These data illustrate the important regulatory role of RE-IIBP in transcriptional regulation, thereby pointing to the important role of HMTase activity in carcinogenesis.
doi:10.1128/MCB.02130-07
PMCID: PMC2268398  PMID: 18172012
15.  X-linked Severe Combined Immunodeficiency Syndrome: The First Korean Case with γc Chain Gene Mutation and Subsequent Genetic Counseling 
Journal of Korean Medical Science  2004;19(1):123-126.
X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the γc chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for γc chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the γc chain gene is useful for definite diagnosis and genetic counseling for X-SCID.
doi:10.3346/jkms.2004.19.1.123
PMCID: PMC2822247  PMID: 14966353
Severe Combined Immunodeficiency; Genetic Diseases, X-linked; Mutation; Genetic Counseling; Korea
16.  Autologous stem cell transplantation for the treatment of neuroblastoma in Korea. 
Journal of Korean Medical Science  2003;18(2):242-247.
Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
PMCID: PMC3055035  PMID: 12692423
17.  Allogeneic peripheral blood stem cell rescue of late graft failure after bone marrow transplantation in patients with aplastic anemia. 
Journal of Korean Medical Science  2002;17(4):468-474.
We investigated the effect and outcome of allogeneic peripheral blood stem cell (PBSC) rescue for aplastic anemia (AA) patients with graft failure after allogeneic bone marrow transplantation (BMT). Seven (28%) of 25 AA patients who received BMT from HLA-identical sibling donors developed late graft failure at a median of 7 months (range, 2.0-9.3 months) after transplantation. The patients with graft failure were treated with PBSC collected from the original donor after mobilization with granulocyte-colony stimulating factor (G-CSF). The median boost dose of peripheral blood mononuclear cells was 3.1 x 10(8)/kg (range, 1.4-11.9 x 10(8)/kg). Median times to reach an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 50 x 10(9)/L were 7 days (range, 4-14 days) and 9 days (range, 3-41 days), respectively. There was sustained graft function in 6 of 7 patients, with a median follow-up duration of 3.3 yr (range, 1.0-6.2 yr). Grade-I acute graft-versus-host disease (GVHD) occurred in 2 patients, while extensive chronic GVHD developed in 3 patients. This report shows that G-CSF-mobilized allogeneic PBSC rescue is very effective in achieving complete and sustained engraftment in patients with AA after graft failure. However, more efficacious measures to prevent extensive chronic GVHD remain to be developed.
PMCID: PMC3054912  PMID: 12172040
18.  X-linked hyper-IgM syndrome associated with Cryptosporidium parvum and Cryptococcus neoformans infections: the first case with molecular diagnosis in Korea. 
Journal of Korean Medical Science  2002;17(1):116-120.
X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder, caused by mutations of the gene encoding CD40 ligand (CD40L; CD154). We report the clinical manifestations and mutational analysis of the CD40L gene observed in a male patient from a XHIM family. Having hypogammaglobulinemia and elevated IgM, the 3-yr-old boy exhibited the characteristic clinical features of XHIM. The patient suffered from frequent respiratory infections, and chronic enteritis caused by Cryptosporidium parvum. In addition, a lymph node biopsy and a culture from this sample revealed C. neoformans infection. Activated lymphocytes from the patient failed to express CD40L on their surface as assessed by flow cytometry and a missence mutation (W140R) was found at the XHIM hotspot in his CD40L cDNA to confirm the diagnosis. Genetic analysis of the mother and sister showed a heterozygote pattern, indicating carrier status. To our knowledge, this is the first report on the molecular diagnosis of an XHIM patient in Korea.
PMCID: PMC3054829  PMID: 11850600

Results 1-18 (18)