• Genomics & Informatics
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• v.11 no.1
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• pp.46-51
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• 2013

Normal-karyotype acute myeloid leukemia (NK-AML) is a highly malignant and cytogenetically heterogeneous hematologic cancer. We searched for somatic mutations from 10 pairs of tumor and normal cells by using a highly efficient and reliable analysis workflow for whole-exome sequencing data and performed association tests between the NK-AML and somatic mutations. We identified 21 nonsynonymous single nucleotide variants (SNVs) located in a coding region of 18 genes. Among them, the SNVs of three leukemia-related genes (MUC4, CNTNAP2, and GNAS) reported in previous studies were replicated in this study. We conducted stepwise genetic risk score (GRS) models composed of the NK-AML susceptible variants and evaluated the prediction accuracy of each GRS model by computing the area under the receiver operating characteristic curve (AUC). The GRS model that was composed of five SNVs (rs75156964, rs56213454, rs6604516, rs10888338, and rs2443878) showed 100% prediction accuracy, and the combined effect of the three reported genes was validated in the current study (AUC, 0.98; 95% confidence interval, 0.92 to 1.00). Further study with large sample sizes is warranted to validate the combined effect of these somatic point mutations, and the discovery of novel markers may provide an opportunity to develop novel diagnostic and therapeutic targets for NK-AML.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4295-4299
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• 2013

Background: Pretreatment serum p53 and epidermal growth factor receptor (EGFR) were assessed using enzyme-linked immunosorbent assay (ELISA) in patients with acute leukemia to analysis their roles in characterization of different subtypes of the disease. Materials and Methods: Serum samples from thirty two patients with acute myeloid leukemia (AML) and fourteen patients with acute lymphoid leukemia (ALL) were analysed, along with 24 from healthy individuals used as a control group. Results: The results demonstrated a significant increase of serum p53 and EGFR in patients with AML (p<0.0001) compared to the control group. Also, the results showed a significant increase of both markers in patients with ALL (p<0.05, p<0.0001 respectively). Sensitivities and specificities for these variables were 52% and 100% for p53, and 73.9%, 95.8% for EGFR. Serum p53 and EGFR could successfully differentiate between M4 and other AML subtypes, while these variables failed to discriminate among ALL subtypes. A positive significant correlation was noted between p53 and EGFR. Negative significant correlations were observed between these variables and both of hemoglobin (Hg) content and RBC count. Conclusions: Mutant p53 and EGFR are helpful serological markers for diagnosis of patients with AML or ALL and can aid in characterization of disease. Moreover, these markers may reflect carcinogenesis mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.369-372
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• 2016

Background: Acute myeloid leukemia is an acquired clonal heterogeneous stem cell disorder. Hence, various parameters are sought out to categorize this disease into subtypes, so that as a consequence specific treatment modalities can be offered. Conventionally, the practically used method for classification utilizes French American British (FAB) criteria based on morphology and cytochemistry. The aim of present study was to determine the current spectrum of AML sub types in patients in Karachi. Materials and Methods: This single centre cross sectional study was conducted at Liaquat National Hospital, Karachi, extending from January 2010 to December 2014. Data were retrieved from archives were analyzed with SPSS version 22. Results: A total of 125 patients were diagnosed at our institution with de novo AML during five years period, 76 males and 49 females. Median age was 34.5 years. AML-M1 was the predominant FAB subtype (23.2%) followed by M2 (18.4%), M3 and M4 (16% each), M0 (14.4%), M5 (7.2%), M6 (3.2%) and M7 (1.6%). Conclusions: AML in Pakistani patients is seen in a relatively young population. The most common FAB subtype observed in our study was acute myeloblastic leukemia, without maturation (M1).

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5615-5620
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• 2013

Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a molecular chaperone and is mostly found in nucleoli. NPM also involved in the maturation of preribosomes and duplication of centrosomes. Furthermore, it is also active in control and regulation of the ARF-p53 tumor suppressor pathway. A high rate of incidence and prognostic involvement is reported by various authors in AML patients. In AML it behaves as a favorable prognostic marker. NPM mutations are more frequently associated with normal-karyotype AML and are usually absent in patients having abnormal or poor cytogenetic. NPM mutations are not frequent in other hematopoietic tumors. Two main types of mutations have been described to date. Both of these cause abnormal cytoplasmic localization of NPM1. Their high incidence rate in normal karyoptype and their favorable nature m ake those mutations hot spot or front face mutations which should be checked before treatment starts.

• Journal of Korean Dental Science
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• v.15 no.2
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• pp.141-146
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• 2022

Leukemia is a neoplastic disease with an excessive proliferation of immature white blood cells and their precursors. Common oral manifestations of acute myeloid leukemia (AML) include ulceration, petechiae, spontaneous bleeding, and gingival hyperplasia. The estimated prevalence of AML is 19 per 100,000 populations, the median age of diagnosis is over 65 years, and of all the subtypes of leukemia, AML accounts for the highest percentage of leukemic deaths. The purpose of this study is to report the case of a 77-year-old female patient, who visited our outpatient clinic due to consistent inflammatory findings. Though she received surgical treatment, she was diagnosed with AML by chance after a preoperative blood test. We also discuss the necessity of performing a preoperative blood test prior to invasive dental procedures such as tooth extraction or biopsy.

• BMB Reports
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• v.40 no.5
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• pp.765-772
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• 2007

Eosinophils act as effectors in the inflammatory reactions of allergic diseases including atopic dermatitis. Atopic dermatitis patients and others with allergic disorders suffer from eosinophilia, an accumulation of eosinophils due to increased survival or decreased apoptosis of eosinophils. In this study, a differential phosphoproteome analysis of AML14.3D10 eosinophil cell line after treatment with IL-5 or dexamethasone was conducted in an effort to identify the phosphoproteins involved in the proliferation or apoptosis of eosinophils. Proteins were separated by 2-DE and alterations in phosphoproteins were then detected by Pro-Q Diamond staining. The significant quantitative changes were shown in nineteen phosphoproteins including retinoblastoma binding protein 7, MTHSP75, and lymphocyte cytosolic protein 1. In addition, seven phosphoproteins including galactokinase I, and proapolipoprotein, were appeared after treatment with IL-5 or dexamethasone. Especially, the phospho-APOE protein was down-regulated in IL-5 treated AML14.3D10, while the more heavily phosphorylated APOE form was induced after dexamethasone treatment. These phosphoproteome data for the AML14.3D10 cell line may provide clues to understand the mechanism of eosinophilia as well as allergic disorders including atopic dermatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1399-1404
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• 2016

We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC) and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients with AML and 24 healthy volunteers were assessed. We used an enzyme-linked immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in urine. Values were higher in patients with ccRCC than in those with AML and in healthy volunteers. High levels were associated with pathologic stage, lymph node status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein beta/alpha were significantly increased in patients with small-sized carcinoma, irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in patients with AML. This study is the first to report that increased expression of 14-3-3 protein beta/alpha in urine is associated with advanced stage and poor survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha may differentiate AML from RCC, even when small sized. These results suggest that examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and prognostic marker in patients with ccRCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3941-3944
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• 2015

Background: Aberrant expression of HOX gene expression has been observed in cancer. The purpose of this study was to investigate the alteration of HOXA5 and HOXA9 expression and their clinical significance in acute meloid leukemia (AML). Materials and Methods: The expression of HOXA5 and HOXA9 genes of bone marrow samples from 75 newly diagnosed AML patients and 22 healthy controls for comparison were examined by Real-time quantitative PCR (RQ-PCR) assay. Statistical analysis was conducted to evaluate HOXA5 and HOXA9 expression as possible biomarkers for AML. Results: The results showed that the complete remission rate (52.6%) of the patients who highly expressed HOXA5 and HOXA9 was significantly lower than that (88.9%) in patients who lowly express the genes (P=0.015). Spearmann correlation coefficients indicated that the expression levels for HOXA5 and HOXA9 genes were highly interrelated (r=0.657, P<0.001). Meanwhile, we detected significant correlations between HOXA9 expression and age in this limited set of patients (P=0.009). Conclusions: The results suggest a prognostic impact of increased expression of HOXA5 and HOXA9 in AML patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1823-1829
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• 2014

Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to the development of acquired chemoresistance. However, the molecular mechanisms are not fully clear. Therefore, we investigated a possible correlation of mRNA expression of HIF-$1{\alpha}$ and GLUT1 with chemoresistance in acute myeloid leukemia (AML). Methods: Bone marrow samples were obtained from newly diagnosed and relapsed AML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1 or HIF-$1{\alpha}$ gene expression in an AML cell line and HIF-$1{\alpha}$ and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR). Results: High levels of HIF-$1{\alpha}$ and GLUT1 were associated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 by RNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparable with RNA interference for the HIF-$1{\alpha}$ gene. Conclusions: Our data revealed that over-expression of HIF-$1{\alpha}$ and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4869-4872
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• 2015

Background: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. Materials and Methods: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. Results: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value = 0.008) and white blood cell count (p-value = 0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value = 0.374). Conclusions: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.