• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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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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• 제41권5호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4581-4585
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• 2012

Fms-like tyrosine kinase 3 (FLT3) performs a vital role in the pathogenesis of hematopoietic malignancies. Therefore in recent times, the focus of several studies was on use of FLT3 as a prognostic marker. The present study investigated the molecular characterization and incidence of FLT3 mutations in acute leukemia patients in Pakistan. A total of 55 patients were studied, of which 25 were suffering from acute lymphoblastic leukemia (ALL) and 30 were suffering from acute myeloid leukemia (AML). The polymerase chain reaction demonstrated FLT3/ITD mutations in 1 (4%) of 25 ALL patients, a male with the L2 subtype. In AML cases the rate was 4 (13.3%) of 30, three males and one female. The AML-M4 subtype was found in three and the AML M2 subtype in the other. In the AML cases, a statistically significant (p=0.009) relationship was found between WBC (109/L) and FLT3/ITD positivity. However, no significant relationship was found with other clinical parameters (p>0.05). In acute myeloid leukemia (AML) $FLT3/ITD^+$ mutation was more prevalent in elderly patients 31-40 age groups, 21-30 and 51-60 age groups respectively. In acute lymphoblastic leukemia (ALL) statistically no significant relationship was found between clinical features and FLT3/ITD positivity (p>0.05). However, in acute lymphoblastic leukemia (ALL) $FLT3/ITD^+$ mutation was more commonly found in age groups of 21-30.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3861-3864
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• 2013

Glutathione S-transferase (GST) enzyme levels are associated with risk of many cancers, including hematologic tumours. We here aimed to investigate the relationships between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of AML. Genotyping of GSTs was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method in 163 cases and 204 controls. Individuals carrying null GSTT1 genotype had a 1.64 fold risk of acute leukemia relative to a non-null genotype (P<0.05). A heavy risk was observed in those carrying combination of null genotypes of GSTM1 and GSTT1 and GSTP1 Val allele genotypes when compared with those carrying wild genotypes, with an OR (95% CI) of 3.39 (1.26-9.26) (P<0.05). These findings indicate that genetic variants of GST and especially the GSTT1 gene have a critical function in the development of AML. Our study offers important insights into the molecular etiology of AML.

• BMB Reports
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• 제36권4호
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• pp.387-389
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• 2003

The young developing leaves of willow (Salix safsaf, Salicaceae) trees have antileukemic activity. After a 24-h incubation in vitro, the crude water extracts of the leaves killed a majority of the blasts of acute myeloid leukemia (AML, 73.8%).

• Genomics & Informatics
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• 제4권3호
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• pp.97-102
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• 2006

In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. Methods: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. Results: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER<0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. Conclusion: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.

• 한국임상약학회지
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• 제19권2호
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• pp.89-95
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• 2009

Gemtuzumab ozogamicin (GO) is an antibody-targeted chemotherapeutic agent consisting of calicheamicin, a potent cytotoxic antibiotic linked to a recombinant humanized anti CD33 monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). GO is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. GO has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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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.

• 한국임상약학회지
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• 제28권3호
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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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• 제17권12호
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• pp.5173-5177
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• 2016

Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.