• Radiation Oncology Journal
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• v.32 no.3
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• pp.198-207
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• 2014

Purpose: To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. Materials and Methods: From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. Results: The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). Conclusion: The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4315-4320
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• 2012

Background: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. Aim of the study: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. Results: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR=6.807, 95% CI=1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value=0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. Conclusion: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.181-187
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• 2018

Background: Posaconazole is a broad-spectrum triazole antifungal agent and the most recommended prophylactic antifungal agent for patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. In this study, we evaluated the status and effectiveness of posaconazole as a prophylactic antifungal agent in pediatric patients receiving induction chemotherapy for AML. Methods: We retrospectively reviewed the electronic medical records of 36 pediatric patients with AML (between January 2013 and September 2017) at the Yonsei University Health System. Invasive fungal disease (IFD) was assessed as the primary endpoint of prophylactic antifungal effect. The secondary endpoints were incidence of fever, persistent fever despite the use of broad-spectrum antibiotics for 72 h, alteration of antifungal agent, intensive care unit admission, and death within 100 days. Results: Among the 36 patients, 18 patients used posaconazole, 12 were treated with suspension formula, and 6 of them were treated with tablets. Eighteen patients did not use antifungal agents prophylactically. The mean number of days of posaconazole administration was $26.8{\pm}16days$. IFD occurred in 2/18 (11.1%) patients in the no prophylaxis group and in 1/18 (5.6%) patients in the posaconazole group (p=0.49). Conclusion: Posaconazole is expected to be useful for the prevention of IFD in pediatric patients with AML undergoing induction chemotherapy. Prospective studies of the effectiveness of posaconazole prophylaxis should be conducted in more pediatric patients in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.895-898
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• 2014

Objectives: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. Methods: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. Results: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (${\chi}^2$ = 0.704, P = 0.703) based on risk stratification. Conclusion: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1089-1092
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• 2013

Background: Elderly patients with acute myeloid leukemia (AML) have a poor outcome because of co-morbidities, poor tolerance to intensive chemotherapy and inherently more resistant disease. Clofarabine is a second generation nucleoside analogue which has shown promising activity in elderly patients with AML. This study was conducted to review the outcome of treatment with clofarabine in a group of such patients. Methods: The records of 5 elderly patients who were diagnosed to have AML and treated with clofarabine over a 12 month period were reviewed retrospectively. Results: There were 2 female and 3 male patients with a median age of 68 years (range 65-82). At the time of treatment, 2 patients had newly diagnosed AML not considered suitable for intensive therapy, while 3 patients had partial or no response to conventional chemotherapy. The overall response rate was 100%, all patients achieving a complete remission. Induction and consolidation were well tolerated. All patients developed neutropenia with a median duration of 20 days (range 17-42). One patient developed hand and foot syndrome and a generalized rash but recovered. There was no mortality and all patients remained in remission after a median follow-up of 5.2 months (Range 3-10). Conclusion: Clofarabine (alone or in combination) is active in elderly AML patients with an acceptable safety profile and should be considered a potential option in this group.

• Molecules and Cells
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• v.41 no.5
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• pp.465-475
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• 2018

The advent of massively parallel sequencing, also called next-generation sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AML-related genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as "hot-zone" analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.

• Molecules and Cells
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• v.46 no.10
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• Journal of Korea Multimedia Society
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• v.21 no.10
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• pp.1150-1161
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• 2018

Classification is widely used in medical images to categorize patients and non-patients. However, conventional classification requires a complex procedure, including some rigid steps such as pre-processing, segmentation, feature extraction, detection, and classification. In this paper, we propose a novel convolutional neural network (CNN), called LeukemiaNet, to specifically classify two different types of leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and non-cancerous patients. To extend the limited dataset, a PCA color augmentation process is utilized before images are input into the LeukemiaNet. This augmentation method enhances the accuracy of our proposed CNN architecture from 96.9% to 97.2% for distinguishing ALL, AML, and normal cell images.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.677-684
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• 2016

Background: Acute lymphoblastic leukemia (ALL) is a heterogeneous disease which requires a risk-stratified approach for appropriate treatment. Specific chromosomal translocations within leukemic blasts are important prognostic factors that allow identification of relevant subgroups. In this study, we developed a multiplex RT-PCR assay for detection of the 4 most frequent translocations in ALL (BCR-ABL, TEL-AML1, MLL-AF4, and E2A-PBX1). Materials and Methods: A total of 214 diagnosed ALL samples from both adult and pediatric ALL and 14 cases of CML patients (154 bone marrow and 74 peripheral blood samples) were assessed for specific chromosomal translocations by cytogenetic and multiplex RT-PCR assays. Results: The results showed that 46 cases of ALL and CML (20.2%) contained the fusion transcripts. Within the positive ALL patients, the most prevalent cryptic translocation observed was mBCR-ABL (p190) at 8.41%. In addition, other genetic rearrangements detected by the multiplex PCR were 4.21% TEL-AML1 and 2.34% E2A-PBX1, whereas MLL-AF4 exhibited negative results in all tested samples. Moreover, MBCR-ABL was detected in all 14 CML samples. In 16 samples of normal karyotype ALL (n=9), ALL with no cytogentic result (n=4) and CML with no Philadelphia chromosome (n=3), fusion transcripts were detected. Conclusions: Multiplex RT-PCR provides a rapid, simple and highly sensitive method to detect fusion transcripts for prognostic and risk stratification of ALL and CML patients.

• Biomedical Science Letters
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• v.24 no.4
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• pp.426-429
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• 2018

Chronic eosinophilic leukemia (CEL) is characterized by eosinophilia and organ damage. Imatinib is widely used for treating CEL, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Unfortunately, the cancer cells gain resistance against the drug after prolonged molecular-targeted therapies. Imatinib-resistant EoL-1 (EoL-1-IR) cells were produced from chronic eosinophilic leukemia cells (EoL-1) after treatment with imatinib for a long duration. Two-dimensional electrophoresis (2-DE) analysis revealed numerous protein variations in the EoL-1 and EoL-1-IR sub-types. Compared to the EoL-1 cells, expression levels of TIP49, RBBP7, ${\alpha}$-enolase, adenosine deaminase, C protein, galactokinase, eukaryotic translation initiation factor, $IFN-{\gamma}$, and human protein homologous to DROER were increased, whereas core I protein, proteasome subunit p42, heterogeneous ribonuclear particle protein, chain B, and nucleoside diphosphate were decreased in the EoL-1-IR cells. Taken together, these results contribute to understanding the pathogenic mechanism of drug-resistant diseases.