背景尽管慢性粒细胞白血病(CML)遗传学有进展,一氧化氮(NO)和硫化氢(H2S)基因突变的作用及其与凋亡基因的关系尚不清楚。因此,这项研究使用Sanger测序和下一代测序(NGS)调查了NO和H2S产生基因突变及其与凋亡基因的相互作用。方法进行全血细胞计数(CBC)以测量白细胞的总数,而IL-6水平在对照和CML患者中使用ELISA技术进行评估。Sanger测序用于分析CTH和NOS3基因的突变,而NGS用于检查所有染色体上的突变。结果CML患者的白细胞(WBC)和粒细胞计数明显高于对照组(p<0.0001),和单核细胞计数类似地更高(p<0.05)。白细胞介素-6(IL-6)水平在CML患者中显著高于对照组(p<0.0001),表明可能与CML病因或进展有关。已经在这两个基因中发现了多个突变,特别是在CTH外显子12和NOS3基因VNTR中,T786C,和G894T。本研究还使用IL-6测定法测量IL-6浓度,确定其作为CML预后诊断的潜力。白细胞计数,粒细胞计数,和中档绝对计数,或MID计数,CML患者明显高于正常对照组。NGS在CML患者中鉴定出1643个体细胞和性染色体异常和439个活跃表达的基因。与其他数据库相比,该发现暗示了CML发展中BCR-ABL1突变之外的基因组景观。结论总之,本研究通过鉴定NO-和H2S产生基因的突变及其与凋亡相关基因的复杂联系,促进了对CML遗传特征的理解.通过Sanger测序和NGS获得的全面遗传图谱为确定CML的治疗和个性化治疗的新目标提供了可能性。因此有助于血液病的发展。
Background Despite advances in chronic myeloid leukemia (CML) genetics, the role of nitric oxide (NO) and hydrogen sulfide (H2S) gene mutations and their relationship to apoptotic genes is unclear. Therefore, this study investigated NO- and H2S-producing genes\' mutations and their interactions with apoptotic genes using Sanger sequencing and next-generation sequencing (NGS). Methodology A complete blood count (CBC) was carried out to measure the total number of white blood cells, while IL-6 levels were assessed in both control and CML patients using an ELISA technique. Sanger sequencing was used to analyze mutations in the CTH and NOS3 genes, whereas NGS was applied to examine mutations on all chromosomes. Results White blood cell (WBC) and granulocyte counts were significantly higher in CML patients compared to controls (p<0.0001), and monocyte counts were similarly higher (p<0.05). Interleukin-6 (IL-6) levels were significantly elevated in CML patients than controls (p<0.0001), indicating a possible link to CML etiology or progression. Multiple mutations have been identified in both genes, notably in CTH exon 12 and the NOS3 genes VNTR, T786C, and G894T. This study also measured IL-6 concentrations using IL-6 assays, identifying its potential as a CML prognostic diagnostic. WBC counts, granulocyte counts, and mid-range absolute counts, or MID counts, were significantly higher in CML patients than in normal control individuals. NGS identified 1643 somatic and sex chromosomal abnormalities and 439 actively expressed genes in CML patients. The findings imply a genomic landscape beyond the BCR-ABL1 mutation in CML development compared to other databases. Conclusion In conclusion, this study advances the understanding of the genetic characteristics of CML by identifying mutations in the NO- and H2S-producing genes and their complex connections with genes involved in apoptosis. The comprehensive genetic profile obtained by Sanger sequencing and NGS provides possibilities for identifying novel targets for therapy and personalized treatments for CML, therefore contributing to developments in hematological diseases.