Significance of OCT3/4 and SOX2 antigens expression by leukemic blast cells in adult acute leukemia.

OBJECTIVE: This study aimed to address the prognostic impact of SOX2 and OCT3/4 expression on adult acute leukemia patients' outcomes. METHODS: SOX2 and OCT3/4 expression by blast cells were evaluated by flow cytometry in 80 acute leukemia patients and 8 healthy controls. RESULTS: Baseline SOX2 and OCT3/4 expression were significantly higher in both ALL (P = < 0.001, P = 0.005 respectively) and AML patients (P < 0.001, P = 0.003 respectively) as compared to control, and decline at complete remission (CR) and elevated again at relapse. High SOX2 and OCT3/4 levels were significantly correlated with the presence of adverse risk stratification parameters. CONCLUSION: Our findings indicated that both SOX2 and OCT3/4 could serve as biomarkers that could improve risk stratification of acute leukemia patients. Also, both SOX2 and OCT3/4 might be a therapeutic target, especially in resistant acute leukemia.

Impact of Nanoparticles Additions on the Strength of Dental Composite Resin.

Objective: This study aimed to evaluate the effect of nanoparticles, zirconium dioxide (ZrO2), titanium dioxide (TiO2), and silicon dioxide (SiO2), on flexural strength (FS), hardness, and wear resistance of light cured dental composite resin. Materials and Methods: 210 rectangular and disc-shaped composite resin specimens were fabricated with dimensions (25 × 2 × 2 ± 0.03 mm) and (6×4 ± 0.03 mm) for FS, hardness, and wear resistance, respectively (70/test). Specimens of each test were divided according to nanofillers into four groups, unmodified as control, ZrO2 (Z), TiO2 (T), and SiO2 (S) groups; each one was further subdivided into two subgroups according to nanoparticles concentration, 3wt.% and 7wt.% (Z3, Z7, T3, T7, S3, and S7), 10 specimens of each subgroup. A3-point bending test and Vickers hardness test were used for FS and hardness measurements, respectively. Wear resistance was evaluated by the differences in surface roughness of tested specimens before and after wear test. Two-way and 1-way ANOVA and Bonferroni's post hoc tests were done for data analysis (α = 0.05). Results: Two-way ANOVA for FS and wear resistance showed that there was a significant interaction between type of nanoparticles and concentration of nanoparticles (p < 0.001) while two-way ANOVA for hardness showed that both type of nanoparticles and concentration of nanoparticles had a significant effect (p < 0.001), while the effect of their interaction was not statistically significant (p=0.142). 1-way-ANOVA test showed significant increase in FS and wear resistance for all tested groups (p < 0.001 and p < 0.001, respectively) except T7 and S7. Also, there was a significant enhancement in hardness for all tested groups (p < 0.001). Conclusion: Modification of light cured composite resin with certain amounts of nanoparticles (3% and 7% of ZrO2 and 3% of TiO2 and SiO2) can be beneficial in improving flexural strength and wear resistance while hardness of composite resin was increased with all NPs additions.

Comparative Effect of Incorporation of ZrO2, TiO2, and SiO2 Nanoparticles on the Strength and Surface Properties of PMMA Denture Base Material: An In Vitro Study.

Objective: This study aimed to investigate the effects of nanoparticles (zirconium dioxide (ZrO2), titanium dioxide (TiO2), and silicon dioxide (SiO2)) on the flexural strength, impact strength, hardness, and wear resistance of the acrylic resin denture base material. Materials and Methods: Acrylic resin specimens were fabricated in dimensions according to American Dental Association (ADA) specifications per test. Specimens were divided according to nanofiller into four groups; unmodified as control, ZrO2 (Z), TiO2, (T), and SiO2 (S) groups. Each one was subdivided into two subgroups according to nanoparticle concentrations; 3% and 7% (Z3, Z7, T3, T7, S3, and S7). A 3-point bending test, Charpy impact test, and Vickers hardness test were used for flexural strength, impact strength, and hardness measurements, respectively. Wear resistance was measured by the differences in surface roughness of tested specimens before and after the wear test. A scanning electron microscope was used to assess nanoparticle specifications and distributions and for fracture surfaces analysis. ANOVA, Bonferroni's post hoc test, and the Kruskal-Wallis test were applied for data analysis (α = 0.05). Results: Regarding the flexural and impact strength, there was a statistically remarkable increase for all tested groups compared with the control group, except for the T7 and S7 groups (P value <0.001, effect size = 0.893) and (P value <0.001, effect size = 0.759), respectively. There was a statistically significant improvement in the hardness of all tested groups compared with the control group (P value <0.001, effect size = 0.67) except T3 and S3. Regarding wear, a statistically significant enhancement was noticed in the wear resistance of all tested groups (P value <0.001, effect size = 0.685), except for the T7 and S7 groups. Conclusion: The flexural strength, impact strength, and wear resistance improved with both concentrations of ZrO2 and low TiO2 and SiO2 concentrations. The hardness increased with both concentrations of ZrO2 and high TiO2 and SiO2 concentrations.

Microbiological evaluation for antifungal activity of some metal oxides nanofillers incorporated into cold cured soft lining materials: clinical based study / Avaliação microbiológica da atividade antifúngica de algumas nanopartículas de óxidos metálicos incorporadas em materiais de revestimento macio curados a frio: estudo clínico

Objetivo: O objetivo do presente estudo foi avaliar a eficácia da adição de nanopartículas de óxido de zircônio (ZrO2), óxido de titânio (TiO2) e óxido de sílica (SiO2) a um material de revestimento macio curado a frio na adesão de Candida albicans (CA). Material e Método: Cinquenta e quatro pacientes foram selecionados e divididos em três grupos de acordo com a modificação do revestimento com nanopartículas de ZrO2, TiO2 e SiO2 (18 cada). Cada paciente recebeu prótese total maxilar com três cavidades, as cavidades foram revestidas com forro macio curado a frio modificado com diferentes concentrações (0%, 3% e 7%) de nanopartículas de óxido metálico. Nos dias 14 e 28, as trocas foram retiradas do local de realinhamento e imediatamente cultivadas para avaliação fúngica. O número de colônias foi contado, os dados coletados e explorados para normalidade usando o teste de Shapiro-Wilk e a transformação logarítmica da contagem de CA foi realizada. ANOVA para medidas repetidas e de uma via (one-way) foram usados, seguidos por teste de Tukey (HSD). O teste t independente foi usado para comparar as contagens de CA em diferentes períodos. Resultados: A adesão do CA foi significativamente diminuída pela adição de nanopartículas de ZrO2, TiO2 e SiO2 em comparação com o grupo controle, também a cobertura antifúngica aumentou com o aumento da concentração de nanopartículas (p <0,005). A maior contagem de CA foi identificada no grupo SiO2 seguido por ZrO2, enquanto TiO2apresentou a menor contagem de CA (p <0,001). Conclusão: Adição de diferentes nanopartículas; ZrO2, TiO2 e SiO2para revestimento macio curado a frio é um método eficaz para reduzir a adesão de CA (AU)

Objective: The aim of the current study was to evaluate the efficacy of addition of zirconium oxide (ZrO2), titanium oxide (TiO2), and silica oxide (SiO2) nanoparticles to cold-cured soft liner on adhesion of Candida albicans (CA). Material and Methods: Fifty-four patients had been selected and divided into three groups according to the modification of soft liner with ZrO2, TiO2, and SiO2 nanoparticles (18 each of). Each patient received maxillary complete denture having three cavities, the cavities were lined using cold cured soft liner modified with different concentration (0%, 3%, and 7%) of metal oxide nanoparticles. On days 14 and 28, swaps were taken out from relining site and immediately cultured for fungal evaluation. The number of colonies were counted, data collected and explored for normality using Shapiro-Wilk test, logarithmic transformation of CA count was performed. Repeated and one-way ANOVA were used followed by Tukey HSD. Independent-t test used to compare between CA counts at different periods. Results: The CA adhesion was significantly decreased by the addition of ZrO2, TiO2 and SiO2 nanoparticles in comparison with control group, also the antifungal coverage increased with nanoparticles concentration increased (P<0.005). The highest CA count was identified in group SiO2 followed by ZrO2, while TiO2 showed the lowest CA count (P <0.001). Conclusion: Addition of different nanoparticles; ZrO2, TiO2 and SiO2 to cold-cured soft liner is an effective method for reducing CA adhesion. (AU)

Influence of Different Beverages on the Color Stability of Nanocomposite Denture Base Materials.

BACKGROUND: The effect of beverages on nanocomposite denture base materials is neglected. Therefore, this study aimed to investigate the influence of different beverages (coffee, tea, cola, and mineral water) on the color stability of nanoparticles-modified denture base materials (DBMs). MATERIALS AND METHODS: A total of 280 specimens (n = 10/group) were prepared from heat-polymerized acrylic resin modified with different concentrations (3% and 7%) of zirconium dioxide (nano-ZrO2), titanium dioxide (nano-TiO2), and silicon dioxide (nano-SiO2) nanoparticles, while 0% was taken as a control. Color change (∆E) of the specimens was evaluated after simulating 6-month immersion time in four commonly used beverages, coffee, tea, cola, and mineral water, as experimental groups. Color stability was measured using a spectrophotometer, and then values were converted to National Bureau of Standards units (NBS units). The one-way ANOVA test was applied to compare color change (ΔE) results followed by Bonferroni's post hoc test (α = 0.05). RESULTS: The results showed that the heat-polymerized acrylic resin modified with different types of nanoparticles showed lower color changes after being immersed in beverage solutions compared to the unmodified group (P < 0.001), so the color stability of heat-polymerized acrylic resin was significantly enhanced by the addition of several nanoparticles; nano-ZrO2 showed the lowest ΔE followed by nano-TiO2 and then nano-SiO2. Regardless of the filler type, 3% concentration showed lower mean ΔE than 7% concentration. Regarding the beverage solutions, the greatest color change was found in the coffee group followed by tea and cola, while water showed the least changes. CONCLUSION: Modification of heat-polymerized acrylic resin with certain amounts of nano-ZrO2, nano-TiO2, and nano-SiO2 may be useful in improving color stability.

Clinical Impact of Percentage of Natural Killer Cells and Natural Killer-Like T Cell Population in Acute Myeloid Leukemia.

BACKGROUND: Natural killer (NK) function defects have been seen in many hematological malignancies, including acute myeloid leukemia (AML). AML is associated with deficient human leukocyte antigen (HLA) expression on leukemia blasts which become targets for killing by NK and natural killer-like T (NKT) cells. However, NK and NKT cells are not effective in killing autologous leukemia blasts, maybe due to number or functional abnormalities. The aim of the work was to detect the number and percentage of NK and NKT cells in patients with AML and the impact of their percentage on the prognosis, response to treatment and survival. METHODS: Bone marrow and peripheral blood samples were collected from 50 adult patients diagnosed as de novo AML who presented to the Hematology Unit in the Oncology Center Mansoura University (OCMU) at time of diagnosis. NK and NKT cells were detected by using immunophenotyping by expression of cell surface and cytoplasmic markers (anti-CD3 fluorescein isothiocyanate (FITC), anti-CD16/56 phycoerythrin (PE)). RESULTS: We observed significant reduction in the median values of NK and NKT cells in AML patients in comparison to normal values. There was an insignificant correlation to response to induction treatment. While a significant correlation to overall survival (OS) (P = 0.03) was observed. The correlation to risk stratification was significant with NK cells (P < 0.001), but not with NKT cells (P = 0.23). CONCLUSION: We concluded that the number and percentage of NK and NKT cells decreased significantly in AML patients and the frequency of NK and NKT cells is inversely proportionate with prognosis and OS in studied AML patients. We recommend correlating both number and function of NK and NKT cells in future studies to help provide a wide field of interest for possibility of demonstrating novel therapies using NK cells for curing AML.

Case report; meta-synchronous triple malignancy in primary diagnosed CML patient.

The diagnosis of different types of cancer in a single patient has been appeared in the field in some case reports involving different categories of cancer types either appeared at the same time (synchronous) or subsequently (meta-synchronous). The aim of this report is to present this interesting case of male patient who was under treatment of CML then T-lymphoblastic lymphoma and HCC discovered subsequently. CML, Lymphoma and HCC are arising from different lines of cells with different biology and cytogenetic criteria. CML and acute lymphoblastic leukemia may occur together in cases of blastic crisis of CML. But, they rarely occur together as separate multiple malignancies especially without any history of exposure to ionizing radiation, chemotherapy or transplantation.

Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia.

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML.

The prevalence and prognostic significance of autoimmune cytopenias in a cohort of Egyptian patients with chronic lymphocytic leukemia.

OBJECTIVE/BACKGROUND: The impact of autoimmune cytopenias (AICs) on the chronic lymphocytic leukemia (CLL) clinical course and its prognostic significance remain a matter of controversial debate. This could be due to exclusion of patients with cytopenia from most clinical trials for this particular complication and the lack of standard diagnostic criteria and treatment approaches. We herein evaluate the prevalence and the prognostic significance of AICs among patients with CLL. METHODS: This is an observational retrospective study. Data on 101 patients with CLL were derived from the Oncology Center, Mansoura University, Egypt, database, which contains information on demographic and clinical characteristics at diagnosis and follow-up records. RESULTS: The prevalence of immune cytopenias was 11.9% among patients studied. Autoimmune hemolytic anemia was the most common autoimmune form in patients with cytopenia due to pure immune etiology (C immune group) with a prevalence of 6.9%. Patients with AICs and those in the C immune subgroup presented with more unfavorable parameters. Besides, patients with AICs showed lesser response to treatment and on restaging after initial treatment, significantly more patients without AICs moved to a more favorable stage. However, no parallel significant difference in the overall survival was found between patients without AICs and those with AICs or with immune and combined or infiltrative cytopenia. CONCLUSION: We have shown a prevalence of 11.8% for AIC among our CLL patients. AIC was associated with unsatisfactory normalization of the hematological parameters even with therapy and lower number of patients with CLL downstaging in comparison with patients without AIC. These results suggest that AIC is a fingerprint of a biologically more aggressive disease even if no significant impact on overall survival was found.

Prognostic impact of CD200 and CD56 expression in adult acute lymphoblastic leukemia patients.

BACKGROUND: The aim of the study is to determine the prognostic relevance of CD200/ CD56 expression in adult acute lymphoblastic leukemia patients. METHODS: The expression of CD200 and CD56 by blast cells was assessed by flow cytometry before the start of chemotherapy in 70 B-ALL patients. RESULTS: Positive expression of CD200 was detected in forty-six patients (66%) and CD56 was detected in 7 patients (10%) out of 70 patients, respectively. Only three patients (4.3%) had co-expression for CD200+ and CD56+. Splenomegaly and thrombocytopenia were frequently observed more in CD200+ patients. Increased frequency of CD34+ was associated with CD200+and CD56+ patients. The CD200+ and CD56+ subgroups of B-ALL patients had inferior OS and disease free survival compared to CD 200- and CD 56- patients. CONCLUSIONS: CD200+ and/or CD56+ positive expression in B-ALL patients at diagnosis is a poor prognostic biomarker. Identification of CD200+ and CD56+ expression at diagnosis is recommended for a better stratification of adult B-ALL patients.

Prognostic impact of CD200 and CD56 expression in pediatric B-cell acute lymphoblastic leukemia patients.

This study aimed to determine the prognostic impact of CD200 and CD56 expression in pediatric B cell acute lymphoblastic leukemia (B-ALL) patients, both of which have been implicated in immune tolerance and previously suggested as independent risk factors. CD200 has a central role in immune tolerance that protects stem cells and other critical tissues from immune damage. The expression of CD200/CD56 in leukemic blasts were assessed in leukemic blasts before chemotherapy in 43 bone marrow (BM) and/or peripheral blood (PB) samples by flow cytometry. Twenty eight of 43 B-ALL cases (65%) showed CD200 positive expression, 5 of 43 cases (11.6%) showed CD56 expression, and only 2 patients (4.7%) expressed both CD200 and CD56. Patients with CD200+ and CD56+ were significantly associated with lower platelet count; less tendency for induction of remission response as compared to negative ones (p = .01 for both). The overall survival (OS) and DFS were significantly shorter in CD200+ and CD56+ cases as compared to those with CD200- and CD56- expression. In conclusion, CD200 and/or CD56 positive expression in B-ALL at diagnosis suggest a poor prognosis and may be associated with biological aggressiveness.

Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism.

OBJECTIVE: to assess the growth and pubertal development among a group of patients with ß-Thalassemia Major (ß-TM) and to evaluate the role of the pituitary gland and liver MRI signal intensity (SI) reduction in assessing and predicting the clinical severity of growth and pubertal dysfunctions. METHODS: Thirty-eight patients with ß-TM were examined and divided into two groups: Group I patients were of normal height and puberty and Group II patients had short statures and hypogonadism. Laboratory investigations included serum ferritin, LH, FSH, prolactin, TSH, and basal and dynamic growth hormones. Pituitary and liver MRIs were performed to assess the pituitary to fat (P/F) and liver to muscle (L/M) signal intensities (SI), respectively. Fifteen healthy and sex- and age-matched subjects were included as controls. RESULTS: Both patient groups had significantly elevated serum ferritin and significantly decreased prolactin and IGF1 compared to control subjects. Group II showed a significant reduction in LH, FSH, and IGF1 and a significant increase in ferritin in comparison with Group I and the control group, and it had a highly significant reduction in both P/F and L/M SI in comparison with Group I (p<0.001 and 0.008, respectively). The reduced P/F ratio was significantly correlated with FSH and LH, and a cutoff for a P/F ratio ≥0.94 was obtained to differentiate between Group I and II. CONCLUSION: MRI in conjunction with the P/F signal intensity ratio is a useful and noninvasive tool for the early diagnosis of pituitary iron overload.

Relation of interleukin-10 Promoter Polymorphisms to Adult Chronic Immune Thrombocytopenic Purpura in a Cohort of Egyptian Population.

BACKGROUND: Adult chronic immune thrombocytopenic purpura (chronic ITP) is an autoimmune multifactorial bleeding disorder that occurs because of enhanced peripheral platelet destruction. Treatment decisions can be challenging because the goal of treatment is to prevent severe bleeding, but the risk of bleeding can be difficult to estimate for any individual patient. OBJECTIVE: This case-control study was planned to investigate the relationship of interleukin (IL)-10 promoter (IL-10-1082, -819 and -592) polymorphisms with the susceptibility, severity and outcome of adult chronic ITP in a cohort of Egyptian population. SUBJECTS AND METHODS: Typing of IL-10 promoter polymorphisms was done using restriction fragment length polymorphism for 62 adult patients with chronic ITP and 73 age- and sex-matched healthy controls. RESULTS: No significant differences were found between ITP patients and controls regarding the frequency of IL-10 promoter genotypes, alleles or haplotypes. IL-10-592 AA genotype and ATA (IL-10-1082, -819 and -592) haplotype were associated with severe ITP (p = 0.003, 0.043, respectively). CONCLUSION: Our findings suggest that the IL-10 promoter polymorphisms are unlikely to affect the development or treatment outcome of chronic adult ITP in Egyptian population, but IL-10-592 AA genotype and IL-10 (-1082, -819 and -592) ATA haplotype may be associated with disease severity. Because ITP is a complex disease, it is recommended that a multicenter study should be done with large sample size and unified typing technique.

Prognostic relevance of Wilms tumor 1 (WT1) gene Exon 7 mutations in-patient with cytogenetically normal acute myeloid leukemia.

This study aimed to assess the prognostic influences of Wilms tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Exon 7 of WT1 was screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, using a high-resolution capillary electrophoresis. Seven out of 82 AML patients (8.3 %) harbored WT1 mutations. There was no significant difference between the mutant WT1 and wild type AML patients as regard age, sex, French-American-British subtypes and the prevalence of success of induction remission therapy (P < 0.5). AML patients with mutant WT1 had shorter overall survival as compared to those patients with wild WT1 (HR = 1.38; 95 % CI 4.79-6.86; P = 0.004). In conclusion, CN-AML patients with WT1 gene mutation have poor clinical outcome. We recommend testing the WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML.

BMI1 gene expression in myeloid leukemias and its impact on prognosis.

BACKGROUND: BMI1 is a polycomb group (PcG) protein and is overexpressed in leukemia. It plays a key role in the self-renewal of stem cells. Leukemic cells lacking BMI1 underwent proliferation arrest and showed signs of differentiation and apoptosis. AIM: This study was aimed to investigate the expression and impact of BMI1 in myeloid leukemias. Expression levels of BMI1 in 100 acute myeloid leukemia (AML), 100 chronic myeloid leukemia (CML) patients and 20 healthy controls were measured by real time quantitative polymerase chain reaction (RQ-PCR). RESULTS: The results showed that the expression of BMI1 was significantly higher in AML and CML versus control subjects (p<0.001 for both). The 2-year overall and disease free survival rates were significantly lower in patients expressing higher BMI1. Multivariate analysis showed that BMI1 was independent prognostic factor for OS for AML cases (p=0.015, HR=3.204, 95% CI=1.250-8.212). Accelerated and blastic phases in CML cases expressed higher BMI1 than chronic phase (p<0.001). CONCLUSION: We concluded that detecting BMI1 is helpful for predicting the survival in AML patients and monitoring the aggressiveness and progression in patients with CML.

Wilms tumor 1 gene mutations in patients with cytogenetically normal acute myeloid leukemia.

OBJECTIVE: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1) mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. MATERIALS AND METHODS: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. RESULTS: Eleven patients out of 82 (13.41%) harbored WT1 mutations. Mutations were detected in exon 7 (n=7), exon 9 (n=2), exon 8 (n=1), and exon 3 (n=1), but not in exons 1 or 2. There was no statistically significant difference between the WT1 mutants and wild types as regards age, sex, French-American-British subtypes, and the prevalence of success of induction remission therapy (p=0.966; 28.6% vs. 29.3%). Patients with WT1 mutations had overall survival lower than patients with the wild type (HR=1.38; 95% CI 4.79-6.86; p=0.004). CONCLUSION: CN-AML patients with WT1 mutations have poor clinical outcome. We recommend molecular testing for WT1 mutations in patients with CN-AML at diagnosis in order to improve risk stratification of those patients.

Prognostic implications of NPM1 mutations and FLT3 internal tandem duplications in Egyptian patients with cytogenetically normal acute myeloid leukemia.

Nucleophosmin (NPM1) and fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) gene mutations represent the most frequent molecular aberrations in patients with cytogenetically normal-acute myeloid leukemia (CN-AML). We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML. NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by polymerase chain reaction and GeneScan assays of bone marrow samples obtained from newly diagnosed 104 CN-AML patients. FLT3-ITD+ and NPM1mut were detected in 36 (34.6%) and 30 (28.8%) out of 104 subjects, respectively, 16 cases (15.4%) had double NPM1mut/FLT3-ITD+. The incidence of FLT3-ITD+ was significantly higher in the NPM1mut group than in the NPM1 wild (NPM1wt) group (P = 0.018). Statistical analysis revealed that isolated NPM1mut group had a better clinical outcomes in terms of higher complete response (CR) rate (P = 0.01) and a trend towards favorable overall survival (OS) and disease-free survival (DFS) (P = 0.28, 0.40, respectively). In contrast, the isolated FLT3-ITD+ group had an unfavorable outcome in terms of lower CR rate (P = 0.12), shorter OS, and DFS (P < 0.0001 for both). The NPM1mut/FLT3-ITD-group had the best OS and DFS, while the NPM1wt/FLT3-ITD+ group had the worst OS and DFS than other groups (NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-) (P < 0.0001 for both). Multivariate Cox regression analysis showed that age and FLT3/ITD+ were independent poor prognostic factors for OS (P = 0.006, <0.0001, respectively), while FLT3/ITD+ was independent predictor for DFS (P = 0.04). However, NPM1mut did not have a significant impact on OS and DFS. In conclusion, adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Patients with NPM1mut/FLT3-ITD- had the best prognosis in terms of higher CR, OS, and DFS, while those with NPM1mut/FLT3-ITD+ had the worst CR rate, and NPM1wt/FLT3-ITD+ had the lowest OS and DFS.

Association of MDR1 gene polymorphism (G2677T) with imatinib response in Egyptian chronic myeloid leukemia patients.

BACKGROUND: Despite the excellent efficacy results of imatinib treatment in CML patients, resistance to imatinib has emerged as a significant problem. Genetic variations in genes involved in drug transportation might influence the pharmacokinetic and metabolism of imatinib. The genotype of a patient is increasingly recognized in influencing the response to the treatment. AIM: To investigate the genotype frequencies of single nucleotide polymorphisms (SNPs) G2677T in CML patients undergoing imatinib treatment to determine whether different genotype pattern of these SNPs have any influence in mediating response to imatinib. METHODS: A total of 96 CML and 90 control samples were analyzed for the human multidrug resistance gene 1 (MDR1) gene polymorphism (G2677T) using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: Genotype distribution revealed a significant lower frequency of TT genotype in CML patients and non-significant difference in the GG, GT genotype frequencies between patients and controls (P = 0.004, 0.138, 0.210, respectively). GG genotype was significantly higher in chronic phase (P = 0.046), while GT genotype was significantly higher in Blastic crisis phase (P = 0.002). There was a significant difference in genotype frequency of G2677T among patients showing response and resistance to imatinib in chronic phase (P = 0.02). TT genotype was associated with complete hematological response (P = 0.01), complete cytogenetic response (P < 0.001), and better molecular response with a significant association (P < 0.001). GT genotype was associated with partial hematological response (P = 0.01) and minor cytogenetic response (P < 0.001). Optimal and suboptimal responses were observed for patients with TT genotype (P = 0.003). Failure of drug response was associated with GT genotype (P = 0.02); however, GG had no association with drug response. Multivariate analysis considered GT genotype as independent risk factor for resistance (P = 0.037), while TT genotype as protective factor against resistance to imatinib (P = 0.008). CONCLUSION: Determination of MDR1 polymorphisms (G2677T) might be useful in response prediction to therapy with imatinib in patients with CML.

Meningioma 1 (MN1) expression: refined risk stratification in acute myeloid leukemia with normal cytogenetics (CN-AML).

Prognostic stratification of cytogenetic normal acute myeloid leukemia (CN-AML) is an area of active research. The aim of this study was to determine the prognostic importance of the meningioma 1 (MN1) gene expression levels in CN-AML. One hundred patients with CN-AML were diagnosed; MN1 expressions were analyzed using quantitative real-time polymerase chain reaction. High expressions were detected in 48 (48%) patients (expression range: 2.35-31.99, mean: 13.9 ± 8.49) in comparison with 52 (52%) patients with low expression (expression range: 0.02-2.3, mean: 0.68 ± 0.77). The course of the disease in patients with high MN1 expression was unfavorable. Patients with high MN1 expression was associated with significant low complete remission rate (62.5 vs. 8.4%, high vs. low MN1, P = 0.001) and high mortality rate (75% vs. 46.1, P = 0.03). AML patients with high MN1 expression tended to be refractory (37.5 vs. 19.2%, P = 0.00) and relapse risk (54.1 vs. 23%, P = 0.02). Multivariable analysis confirmed high MN1 expression as an independent risk factor for disease-free survival and overall survival. In conclusion, MN1 overexpression independently predicts bad clinical outcome in CN-AML patients.

Impact of serum adiponectin and leptin levels in acute leukemia.

Adipocytokines was stated to exert biological effect on tumor cells. Two adipokines, leptin and adiponectin in particular, have come to be recognized for their influence on tumor biology including leukemia. The prognostic effect of leptin and adiponectin concentrations in acute leukemia patients remains to be identified. This study was conducted on 80 acute leukemia patients: 35 acute myeloid leukemia (AML), 45 acute lymphoid leukemia (ALL), and 20 controls of matched age and sex. Leptin and adiponectin were assayed by enzyme-linked immunosorbent assay at diagnosis. Serum leptin levels were significantly higher in ALL patients, and significantly lower in AML patients when compared with normal controls (P = 0.01, P = 0.04 respectively). On the other hand, serum adiponectin levels were significantly lower in AML and ALL patients as compared with normal controls (P = 0.00 for both). No significant differences exist regarding body mass index between acute leukemia patients and normal controls (P > 0.05). Correlation studies revealed that there were significant negative correlations between serum adiponectin levels and bone marrow (BM) blast cells and serum lactic dehydrogenase (sLDH) in acute leukemia groups (r 0.542, P < 0.01, r 0.699, P < 0.001, respectively). Regarding serum leptin levels there were positive significant correlations with BM blast cells (r 0.74, P < 0.01), total WBC counts (r = 0.59, P < 0.05), sLDH (r 0.738, P < 0.01) in ALL group; and significant negative correlations with BM blast cells (r 0.542, P < 0.01) and sLDH in the AML group. Adipocytokines may represent a new non-invasive biomarker in acute leukemia patients. Estimation of adiponectin and leptin serum levels at acute leukemia diagnosis could also be considered as a prognostic marker, which will be used in acute leukemia stratification.