RESUMO
We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3Amut). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3Amut patients. At the time of diagnosis, DNMT3Amut transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3Amut transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3Amut transcript levels were significantly higher in BM than in blood after induction I (P=0.01), induction II (P=0.05), consolidation I (P=0.004) and consolidation II (P=0.008). With regard to the clinically relevant MRD time points, after two cycles of induction and at the end of therapy, DNMT3Amut transcript levels had no impact on the end point remission duration and overall survival. Of note, only a minority of the patients achieved RQ-PCR negativity, whereas most had constantly high DNMT3Amut transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.
Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Leucemia Mieloide Aguda/genética , Adulto , Idoso , DNA Metiltransferase 3A , Feminino , Hematopoese/genética , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasia Residual/genética , Neoplasia Residual/patologia , Prognóstico , Adulto JovemAssuntos
Cromossomos Humanos Par 21/genética , Leucemia Mieloide Aguda/genética , Mutação/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Feminino , Alemanha , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Translocação Genética/genética , Adulto JovemRESUMO
Exaggerated placental site (EPS) reaction is an exuberant physiologic process in which intermediate trophoblasts infiltrate the underlying endometrium and myometrium at the implantation site. During a caesarean section, we noted a polypoid well shaped smooth lesion, about 3 cm in diameter on the anterior wall of the uterus apart from the placenta. The histopathologic examination revealed an exuberant proliferation of trophoblastic cells in the placental site, a low Ki-67 labelling index and the absence of mitotic activity. Distinguishing EPS reaction from the other intermediate trophoblastic tumours is critical, as the latter may likely involve surgical intervention and/or chemotherapy, although no specific treatment and follow-up is required for EPS reaction. It is necessary to be aware of this pathology and take biopsies from suspicious lesions in the placental site for pathologic examination.
Assuntos
Recesariana , Placenta/patologia , Tumor Trofoblástico de Localização Placentária/patologia , Trofoblastos/metabolismo , Adulto , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Discrepância de GDH , Gravidez , Neoplasias UterinasAssuntos
Proteína alfa Estimuladora de Ligação a CCAAT/genética , Mutação em Linhagem Germinativa , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/cirurgia , Síndromes Neoplásicas Hereditárias/genética , Transplante de Células-Tronco de Sangue Periférico , Adulto , Antecipação Genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Terapia Combinada , Feminino , Células-Tronco Hematopoéticas/patologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/cirurgia , Linhagem , Leucemia-Linfoma Linfoblástico de Células Precursoras , Recidiva , Terapia de Salvação , Sobreviventes , Transplante HomólogoRESUMO
PURPOSE OF STUDY: To investigate whether serum levels of leukemia inhibitory factor (LIF), interleukin 10 (IL-10) and interleukin 11 (IL-11) are different in reference to the site of implantation. METHODS: Seventeen patients with laparoscopic diagnoses of tubal ectopic pregnancy (EP) and 19 patients with intrauterine pregnancy delivering healthy term neonates (IUP) were prospectively evaluated for LIF, IL-10 and IL-11 levels. The data were compared by using the Student's t-test, chi-square test, Kruskal-Wallis and the Mann-Whitney U test with Bonferroni's correction (p < 0.05) as appropriate. RESULTS: A statistically significant difference was observed in serum LIF levels between the EP and IUP groups (p = 0.002). Ranges of LIF were 15-300 and 70-1200 ng/ml for the IUP and EP groups, respectively. There were no significant differences between groups in terms of IL-10 and IL-11 levels. CONCLUSION: LIF, but not IL-10 or IL-11, levels may be increased in early tubal ectopic pregnancies when compared to normal intrauterine pregnancies.
Assuntos
Interleucina-10/sangue , Interleucina-11/sangue , Fator Inibidor de Leucemia/sangue , Gravidez Ectópica/sangue , Gravidez/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Estudos ProspectivosRESUMO
This study was designed to analyze the effect of global and gene-specific DNA methylation patterns on the outcome of patients with acute myeloid leukemia (AML). Methylation of CDKN2B (p15), E-cadherin (CDH) and hypermethylated in cancer 1 (HIC1) promoters and global DNA methylation by luminometric methylation assay (LUMA) was analyzed in 107 AML patients and cytogenetic and molecular mutational analysis was performed. In addition, genome-wide promoter-associated methylation was assessed using the Illumina HumanMethylation27 array in a proportion of the patients. Promoter methylation was discovered in 66, 66 and 51% of the patients for p15, CDH and HIC1, respectively. In multivariate analysis, low global DNA methylation was associated with higher complete remission rate (hazard ratio (HR) 5.9, P=0.005) and p15 methylation was associated with better overall (HR 0.4, P=0.001) and disease-free survival (HR 0.4, P=0.016). CDH and HIC1 methylation were not associated with clinical outcome. Mutational status and karyotype were not significantly associated with gene-specific methylation or global methylation. Increased genome-wide promoter-associated methylation was associated with better overall and disease-free survival as well as with LUMA hypomethylation. We conclude that global and gene-specific methylation patterns are independently associated with the clinical outcome in AML patients.
Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Caderinas/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To assess the effects of endometrial thickness and echogenicity on pregnancy and implantation rates in cases using assisted reproductive technology (ART). METHODS: We retrospectively analyzed the data of 241 ART cycles performed at Istanbul Medical Faculty, Reproductive Endocrinology Unit. The cycles were classified into three groups according to ultrasonographic endometrial thickness measurements on the day of hCG application; 51 cases (group 1) < or =8 mm, 182 cases (group 2) between 8-14 mm, and eight cases (group 3) 14 mm. Also the cycles were grouped according to endometrial echogenicity as trilaminar, isoechogenic and hyperechogenic pattern. RESULTS: There was no significant difference in pregnancy rates between the three endometrial thickness groups and echogenic patterns. When conception and non-conception cycles were compared, no significant difference in endometrial thickness was observed (9.88 +/- 1.83 mm vs 9.84 +/- 1.89 mm). CONCLUSION: Ultrasonographic evaluation of endometrial thickness and pattern is not useful in predicting implantation and conception rates in ART cycles.
