RESUMO
Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy that overlaps with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and tends to transform into acute myeloid leukemia (AML). Among cases of CMML, > 90% have gene mutations, primarily involving TET2 (~ 60%), ASXL1 (~ 40%), SRSF2 (~ 50%), and the RAS pathways (~ 30%). These gene mutations are associated with both the clinical phenotypes and the prognosis of CMML, special CMML variants and pre-phases of CMML. Cytogenetic abnormalities and the size of genome are also associated with prognosis. Meanwhile, cases with ASXL1, DNMT3A, NRAS, SETBP1, CBL and RUNX1 mutations may have inferior prognoses, but only ASXL1 mutations were confirmed to be independent predictors of the patient outcome and were included in three prognostic models. Novel treatment targets related to the various gene mutations are emerging. Therefore, this review provides new insights to explore the correlations among gene mutations, clinical phenotypes, prognosis, and novel drugs in CMML.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/genética , Mutação , Proteínas de Transporte/genética , Aberrações Cromossômicas , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Metilação de DNA , DNA Metiltransferase 3A/genética , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Epigênese Genética , Repressão Epigenética , GTP Fosfo-Hidrolases/genética , Genes ras , Tamanho do Genoma , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mielomonocítica Crônica/mortalidade , Proteínas de Membrana/genética , Síndromes Mielodisplásicas/genética , Proteínas Nucleares/genética , Fenótipo , Prognóstico , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Repressoras/genética , Fatores de Processamento de Serina-Arginina/genética , Transdução de Sinais/genéticaRESUMO
Single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B have been reported to be associated with bipolar disorder in European and Japanese populations. We explored the roles of 21 tag SNPs in HTR3A and HTR3B in susceptibility to bipolar disorder in a Chinese cohort. Twenty-one Tag SNPs were genotyped in a study consisting of 130 patients with bipolar disorder, who visited Shandong Mental Health Center between June 2013 and May 2014, and 109 healthy individuals as controls. All of the tag SNPs were genotyped using Sequenom MassArray matrix-assisted laser desorption/ionization time of flight spectrometry. Plink 1.07, Haploview 4.2, and SPSS 20.0 were used for the analysis of the genotypes and the associations of the haplotypes with bipolar disorder. Association analyses of tag SNPs detected significant associations with the A allele in HTR3A rs1176719 (P = 0.030) and the C allele in HTR3A rs1176713 (P = 0.048). Haplotype-based association analyses indicated a statistically significant (P = 0.035) five-SNP haplotype (rs1062613:C, rs11604247:C, rs1176722:G, rs2276302:A, rs1176719:G) of linkage disequilibrium in block 3. Analysis of our small Chinese sample revealed a significant association of HTR3A with bipolar disorder, but yielded no evidence of an association between HTR3B and bipolar disorder. Furthermore, evidence for an association was found for a haplotype of HTR3A. Studies with larger Chinese samples are needed to verify our findings.