• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.221-227
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• 2014

Background: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. Aims: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. Materials and Methods: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Results: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ${\geq}2$ Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Conclusions: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ${\geq}2$ Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.

• 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.13 no.9
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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.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.192-198
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• 2003

Purpose: Current results of autologous stem cell transplantation (SCT) suggest that this procedure may prolong disease free survival In patients with acute myeloid leukemia (AML). Autologous SCT is increasingly used as treatment for AML in first remission. The aim of this study was to evaluate the outcome of autologous SCT for patients with AML in first remission treated by autologous SCT using cytarabine, melphalan and total body irradiation (TBI) as the conditioning regimen. Materials and Methods: Between January 1995 and December 1999, 29 patients with AML in first remission underwent autologous SCT. The median age of patients was 33 years (range, 16 to 47). The conditioning regimen consisted of cytarabine ($3.0\;gm/m^2$ for 3 days), melphalan ($100\;gm/m^2$ for 1 day) and TBI (total 1000 cGy in five fractions over 3 days). Results: The median follow up was 40 months with a range of 3 to 58 months. The 4-year cumulative probability of disease free survival was 69.0%, and median survival was 41.5 months. The 4-year relapse rate was 27.6%. The factor Influencing disease free survival and relapse rate was the French-American-British (FAB) classification ($M_3$ group vs. other groups; p=0.048, p=0.043). One patient died from treatment-related toxicity. Conclusion:: Although the small number of patients does not allow us to draw any firm conclusion, our results were encouraging and suggest that the association of cytarabine, melphalan and TBI as a conditioning regimen for autologous SCT for AML on first remission appears to be safe and effective.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.1
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• pp.79-92
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• 2006

This study was carried out to evaluate antioxidative, cytotoxic and chemosensitizing effects for anti-tumor activities of Naesosungma-tang (NST). The results were as follows ; 1. The oxidative effects were measured by DPPH radical scavenging activity. NST water extract was showed more effective than ethanol extract and also various solvent fractions from NST showed effective in the following order : butanol fraction > ethyl acetate fraction > hexane fraction > aqueous fraction. 2. NST water extract was showed cytotoxic effects on the human cancer cells Calu-6 cell and SNU-601 cell, but not on MCF-7 cell. 3. The viability of cells was measured in 4 kinds of solvent fractions from water extract of NST by MTT assay. The results were as followings : 1) On the NIH3T3 cell, $IC_{50}$ value was $200{\sim}300\;{\mu}g/m{\ell}$ in three fractions except aqueous fraction. 2) On the Caco-2 cell, effective only in the butanol fraction. 3) On the Calu-6 cell, most effective in hexane fraction($IC_{50}:80\;{\mu}g/m{\ell}$) and effective in ethyl acetate and butanol fraction($IC_{50}:100{\sim}120\;{\mu}g/m{\ell}$). 4) On the MCF-7 cell, $IC_{50}$ value was similar in three fractions except aqueous fraction. 5) On the SNU-601 cell, $IC_{50}$ value was within $100\;{\mu}g/m{\ell}$ in three fractions except aqueous fraction. 6) On the HCT-1l6 cell, $IC_{50}$ value was $150{\sim}200\;{\mu}g/m{\ell}$ in three fractions except aqueous fraction. 7) On the AML-2/WT cell, not effective in four kinds of solvent fractions. 4. In combined effects of NST and vincristine on AML-2/D100 cell, water and ethanol extracts of NST and hexane fraction of water extracts of NST more effectively inhibited proliferation of AML-2/D100 cell. These results Suggest that NST has antioxidative and cytotoxic effects against Caco-2, Calu-6, MCF-7, SNU-601, HCT116 and NIH3T3 cell especially Calu-6 and SNU-601 cell, and also chemosensitizing effects against AML-2/D100 cell in combined vincristine.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5251-5256
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• 2016

Background: Diagnostic karyotyping analysis is routinely used in acute myeloid leukemia (AML) clinics. Categorization of patients into risk stratified groups (favorable, intermediate and adverse) according to cytogenetic findings can serve as a valuable independent prognostic factor. Method and Material: A retrospective descriptive study was conducted based on the patient records of newly diagnosed non-M3 AML young adult cases undergoing standard 3+7 i.e, Daunorubicin and Ara-C (DA) as remission induction chemotherapy. Diagnostic cytogenetic analysis reports were analyzed to classify the patients into risk stratified groups according to South West Oncology Group criteria and prognostic significance was measured with reference to achievement of haematological remission after 1st induction chemotherapy. Results:A normal karyotype was commonly expressed, found in 47.2% of patients, while 65% (n=39) appeared to have intermediate risk cytogenetics, and 13.3% (n=8) adverse or unclassified findings. Favourable cytogenetics was least frequent in the patient cohort, accounting for only 8.3 % (n=5).The impact of cytogenetic risk groups on achievement of haematological remission was evaluated by applying Pearson Chi-square, and was found to be non-significant (df=12, p=0.256) but when the outcomes of favourable risk groups with intermediate, adverse and unclassified findings compared, results were highly significant (df=6, p=0.000) for each comparison. In patients of the favourable cytogenetic risk group, HR?? was reported in 40% (n=2/5), as compared to 62.2% (n=23/37) in the intermediate cytogenetic risk group, 57.1% (n=4/7) in the adverse cytogenetic risk group and 28.6% (n=2/7) in hte unclassified cytogenetic risk group. Conclusion: Cytogenetic risk stratification for AML cases following criteria provided by international guidelines did not produce conclusive results in our Pakistani patients. However, we cannot preclude an importance as the literature clearly supports the use of pretreatment karyotyping analysis as a significant predictive marker for clinical outcomes. The apparent differences between Pakistani and Western studies indicate an urgent need to develop risk stratification guidelines according to the specific cytogenetic makeup of South Asian populations.

• Korean Journal of Clinical Laboratory Science
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• v.45 no.3
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• pp.120-123
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• 2013

Leukemia in pregnancy was first reported by Virchow in 1845, and acute Leukemia that occurs with pregnancy is extremely rare. About 350 pregnancies with leukemia have been reported in literature. The incident of acute leukemia during pregnancy has been reported in one case per 100,000 pregnancies case. A 40-year-old patient with 30 weeks of pregnancy, (by promyelocyte which is contained granules and auer rods in the bone marrow and biopsy) was diagnosed with acute promyelocyte leukemia WITH t (15;17) (q22;q12); PML-RARA. (M3) in peripheral blood and bone marrow examination, and gave a birth to the fetus normally, January 24, 2013, after receiving the complete remission decision from the bone marrow, complete blood cell count, PML-RARA PCR test, showed normal findings until March 2013. The treatment of acute leukemia during pregnancy should be considered as treatment of a pregnant mother and the impact on the fetus. Decisions about when and how birth takes place is difficult and has to consider both mother and fetus. It is preferable to start immediate treatment without delay so that the treatment time to achieve complete remission or full recovery of the pregnant mother is longer.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.359-369
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• 1997

We studied the expression of the cell surface antigen associated with myeloid and lymphoid leukemias on bone marrow or peripheral blood blast cells from 153 leukemic patients including 61 cases of acute myelogenous leukemias(AML), 46 of acute lymphocytic leukemias(ALL) and 12 of acute leukemias. They were analyzed by direct or indirect immunofluorescence method for reactivity with the monoclonal antibodies to B cells(CD10, CD19, SmIg), T cells(CD2, CD5, CD7, CD3, CD4, CD8), myeloid antigen(CD13, CD14, CD33, CD61) and a nonspecific antigen, HLA-DR. Lymphoid associated markers detected on AML is CD7 32.8%, CD10 14.8%, CD5 13.1%, CD2 6.6% and CD19 1.6%. TdT was positive in 4.9% of AMLs. Hybrid leukemias were 8 cases out 61 AML cases and were mainly composed of monocytic lineage, M4 and M5a. Myeloid markers detected in ALL were CD13 2.2% and CD33 2.2%. In this study, immunologically classified ALLs were composed of 65.2% of CALLA (+) B precursor type, 10.9% of CALLA (-) B precursor pattern, 8.7% of T cell type, 2.2% of B cell type, 4.5% of mixed lymphoid lineage(B&T), 2.2% of undifferentiated leukemia, and 6.5% of hybrid leukemia. Twelve cases of acute leukemias ware finally diagnosed to be 5 cases of hybrid leukemia, 3 cases of B lineage, 3 case of T lineage and 1 case of mixed lymphoid(B&T) leukemia. In summary, we think the best method for typing acute leukemias is by using a combination of FAB classification and immunophenotying.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.613-618
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• 2005

This study was carried out to examine the effects of gamma irradiation on the cytotoxicity and multidrug-resistance reversing activity of methanol extracts from Coix lachryma-jobi L. var. me-yuen Stapf seed. The seed was irradiated with doses of 1, 4, 8, 16, 32 and 64 Gy of the gamma radiation, and then extracted by methanol. The extracts were examined for cytotoxicity on the human cancer cell lines, MCF-7 (human breast adenocarcinoma pleural effusion), Calu-6 (human pulmonary carcinoma) and SNU-601 (human gastric carcinoma) cells, and investigated for multidrug-resistance reversing activity using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. The growth inhibitory activity of irradiated seed extracts on human cancer cell lines was higher than that of the control. In the case of Calu-6 cell line, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. $IC_{50}$ value in the MCF-7 cell line was measured in the only 8 Gy extract. And in the SNU-601 cell line as Calu-6, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. But the extracts of gamma-irradiated seed over 32 Gy showed little growth inhibitory effect against human cancer cell lines. In this result, 8 Gy extract had significant growth inhibitory in all human cancer cell lines $(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL\;and\;SNU-601:\;683\;{\mu}g/mL)$. The extracts of 4, 8 and 16 Gy strongly potentiated vincristine cytotoxicity in AML-2/D100 cells. The reversal fold (RF) of 4, 8 and 16 Gy extracts was 1.7, 1.8 and 1.6, respectively. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. These results indicate that the above samples would contain some principles which have cytotoxicity and multidrug-resistance reversing activity. Irradiation technology can be applied to promote physiological activities of medicinal plant seeds.

• The Korean Journal of Nuclear Medicine
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• v.35 no.4
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• pp.286-287
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• 2001

A 44 year-old male patient was undergoing diagnosis and therapy for acute myelogenous leukemia (AML, M2). On physical examination a thyroid mass was palpated in the left lower lobe. He had palpitation and intolerance to heat. Thyroid function tests revealed hyperthyroidism; T3: 150ng/dl (N:60-90), fT4: 2.26 ng/dl (N:0.70-1.80), TSH: 0.01 ulU/ml (N:0.25-5.00). Ultrasonography demonstrated a hypoechoic mass with scattered calcifications measuring 2.55 2.03 3.64 cm in size. F-18 FDG camera-based PET scan performed as a follow-up study of AML revealed a focal increased uptake in the left neck, where an autonomous nodule was detected on Tc-99m thyroid scan. After the diagnosis of toxic autonomous nodule, Goetz disease, he underwent surgical nodulectomy. Microscopically, the nodule contained follicular proliferation with degenerative change but without evidence of thyroid carcinoma. Focal uptake in autonomous thyroid nodules is due to increased glycolysis within the nodules.