The role of neutrophils in chronic cough.

Chronic cough is a common disorder lasting more than 8 weeks and affecting all age groups. The evidence supporting the role of neutrophils in chronic cough pathology is based on many patients with chronic cough developing airway neutrophilia. How neutrophils influence the development of chronic cough is unknown. However, they are likely involved in multiple aspects of cough etiology, including promoting airway inflammation, airway remodeling, hyper-responsiveness, local neurogenic inflammation, and other possible mechanisms. Neutrophilic airway inflammation is also associated with refractory cough, poor control of underlying diseases (e.g., asthma), and insensitivity to cough suppressant therapy. The potential for targeting neutrophils in chronic cough needs exploration, including developing new drugs targeting one or more neutrophil-mediated pathways or altering the neutrophil phenotype to alleviate chronic cough. How the airway microbiome differs, plays a role, and interacts with neutrophils in different cough etiologies is poorly understood. Future studies should focus on understanding the relationship between the airway microbiome and neutrophils.

[Expression and Prognostic Value of Metabolism-related Genes in Pediatric Acute Lymphoblastic Leukemia].

OBJECTIVE: To analyze the expression and prognostic value of metabolism-related genes in pediatric acute lymphoblastic leukemia (ALL), and explore the potential prognostic biomarkers or therapeutic targets. METHODS: Transcriptome data from 84 children with B-cell ALL at the time of diagnosis and prior to any treatment were used to analyze the differential gene expression. A prognostic scoring system based on the expression of the metabolism-related genes was constructed using Cox and Lasso regression methods. The prognostic value of the scoring system was further assessed by multivariate Cox regression analysis. Gene set enrichment analysis was carried out by using GSEA software. RESULTS: Among the 933 metabolism-related genes, 14 up-regulated genes and 17 down-regulated genes were identified as differentially expressed genes. In addition, 8 up-regulated genes (ASS1, CKM, PTGES, ADCY5, HNMT, PHGDH, CYP4F3, AADAT) and 4 down-regulated genes (GDA, DHRS9, IDO2, UGT2B4) were selected to establish a novel prognostic scoring system. Patients in the high-risk group showed poorer survival significantly than patients in the low-risk group (P<0.05). The prognostic scoring system was still shown to be an independent prognostic factor for the survival of children with ALL after the clinical characteristics, such as gender, age, white blood cell count at initial diagnosis, cytogenetics and molecular genetics were included (HR=8.906, 95%CI: 3.114-25.470). GSEA results showed that 6 metabolism-related pathways (amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, glyoxylate and dicarboxylate metabolism, pyrimidine metabolism, selenoamino acid metabolism) were enriched in the high-risk group. CONCLUSION: The abnormal metabolism-related gene expression is associated with the clinical outcome of children with ALL, and these results provide potential novel prognostic biomarkers and treatment targets for pediatric ALL.

Decitabine combined with CAG for the treatment of atypical chronic myeloid leukemia: a case report and literature review.

Atypical chronic myeloid leukemia BCR/ABL1 negative (aCML) is a rare hematopoietic stem/progenitor cell disorder characterized by neutrophilia, high rate of transformation to acute myeloid leukemia and poor survival. Currently, there is no consensus on the treatment for aCML. In this study, we report the case of a 52-year-old female aCML patient treated with decitabine in combination with CAG chemotherapy who achieved complete remission after the first course. The patient was subsequently treated with three cycles of the same regimen as consolidation treatment. Approximately two months after the completion of the fourth cycle, the patient was in good general health with less than 0.01% minimal residual leukemic cells. The findings of this case report indicate that decitabine in combination with CAG chemotherapy may be an effective treatment for aCML.

Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report.

As an essential component of consolidation and maintenance therapy for acute lymphoblastic leukemia (ALL), mercaptopurine (6-MP) causes critical myelosuppression. The current study aimed to clarify the reasons for severe myelosuppression and significant hyperpigmentationin a patient with ALL that received consolidation therapy. The present study performed patient NUDT15 testing with fluorescence in situ hybridization and whole-exome sequencing. The results revealed that the patient was a homozygous carrier (415C>T, TT) for rs116855232 (NUDT15). The dose of 6-MP was adjusted down from 30%, with the patient receiving maintenance therapy at 8% of the recommended dose. The homozygous mutant (TT genotype) of NUDT15 may cause hematopoietic toxicity with low doses of 6-MP. NUDT15 genotyping should therefore be performed prior to the administration of thiopurine, the dosage of which requires adjustment.

[Detection and Analysis of T Lymphocyte Subsets and B Lymphocytes in Patients with Acute Leukemia].

OBJECTIVE: To investigate the changes of T lymphocyte subsets, B lymphocyte and NK cells in peripheral blood of patients with acute leukemia at different periods and their significance. METHODS: The peripheral T lymphocyte subsets and B lymphocyte of 95 patients with acute leukemia [(43 cases of acute lymphoblastic leukemia (ALL), 52 cases of acute myeloid leukemia (AML)] and 50 normal people were detected by flow cytometry respectively. RESULTS: The positive rate of CD3+, CD3+CD4+, CD3+CD8+, NK cells and CD4+/CD8+ in the patients with newly diagnosed acute leukemia were significantly lower than those in normal controls (P<0.05) , but increased obviously after complete remission. The positive rate of Treg cells in the patients with newly diagnosed leukemia group was significantly higher than that in normal controls (P<0.01) , but decreased obviously after complete remission. Positive rate of CD3-CD19+ cells in the patients with newly diagnosed acute myeloid leukemia was significantly lower , but higher in the patients with newly diagnosed acute lymphoblastic leukemia than that in normal controls with statistical significant difference (P<0.05) , and increased obviously in the patients with acute myeloid leukemia (P<0.05) after complete remission , but decreased in the patients with acute lymphoblastic leukemia (P<0.01) after complete remission or no-remission. CONCLUSION: Changes of T lymphocyte subsets, B lymphocytes and NK cells in the patients with newly diagnosed acute leukemia are significant, thus the detection of T lymphocyte cell subsets, B lymphocytes and NK cells can provide some evidences. for evaluation of the disease severity, curative efficiency and prognosis of patients with acute leukemia.

[Relation of GSTM1 Polymorphism with Leukemia].

OBJECTIVE: To investigate the relation of GSTM1 polymorphism in leukemia patients with therapeutic efficacy and the main biological characteristics. METHODS: The GSTM1 genotypes were detected by nested PCR; the remission rate after 1 course of treatment and main biological characteristics at occurrence of leukemia were compared between AL patients with different GSTM1 genotypes, and their relation was analyzed. RESULTS: The remission rate and partial remission rate after 1 course of treatment in patients with GSTM1-undeleted genotype were no significantly different from those in patients with GSTM1 null genotype (χ2=0.290, P>0.05). The stratification analysis showed that GSTM1 null genotype was not related with age, sex, WBC count, Hb level, plt count at initial diagnosis and spleen enlargenent or no(P>0.05). The comparison of AML and ALL with GSTM1 null genotype by Log-rank showed that the survival rate was no statistically different between AML and ALL patients(χ2=2.043, P>0.05), while the LDH level in serum of patients with GSTM1-undeleted genotype at initial diagnosis was statistically different from that in patients with GSTM1 null genotype (P=0.001). CONCLUSION: The GSTM1 genotype does not relate with remission and partial remission rates after 1 course treatment of AL patients, but relates with LDH level. GSTM1 null genotype deletion may play a role in risk of leukemia.

[Relationship of MPO and NQO1 gene polymorphisms with susceptibility to acute leukemia].

The aim of this study was to investigate the relationship of the gene polymorphisms of myeloperoxidase (MPO) and NAD (P) H: quinone oxidoreductase 1 (NQO1) with the susceptibility to acute leukemia (AL) in Chinese Gansu population. A 1:1 paired case-control study of 150 patients with acute leukemia and 150 cancer-free inpatients as a control was conducted to detect the polymorphisms of MPO and NQO1 by LDR techniques. The results showed that the MPO-463A genotype frequency in patient group was lower than that in control group, and there was significant difference of MPO (G-463A) genotype between patient group and control group (χ(2) = 11.828, P < 0.05, OR = 0.368, 95%CI = 0.205 - 0.610). The NQO1-609T genotype frequency in patient group was higher than that in control group, and there was significant difference of NQO1 (C-609T) genotype between patient group and control group (χ(2) = 17.931, P < 0.05, OR = 1.428, 95%CI = 1.237 - 3.339). The combined gene analysis showed that the AML risk in patients carrying the wild genotypes of MPO and NQO1 was dropped to 33.6%. It is concluded that the MPO and NQO1 gene polymorphisms are associated with susceptibility to AL. The AL risk may decrease in patients carrying MPO (G-463A) mutant gene (GA/AA), while the AL risk may increase in patients carrying NQO1 (C-609T) mutant gene (TC/TT). The combined effect of MPO and NQO1 wild genotypes may further decrease AL risk.

[Relation of GSTP1 and CYP2E1 polymorphisms with susceptibility to acute leukemia].

This study was aimed to investigate the relation of glutathione S-transferase pI (GSTP1) and cytochrome P450 enzyme 2E1 (CYP2E1) gene polymorphisms with the susceptibility to acute leukemia (AL) in Chinese population. The GSFP1 and CTP2E1 gene polymorphisms in 150 patients with AL and 150 patients with non-hematological diseases or non-tumor as controls were detected by means of case-control paired 1:1 method and ligase detection reaction (LDR) techniques. The results indicated that the frequently of G allele and Ile/Val + Val/Val of GSTP1 gene (26.7%and 44% respectively) in AL group were higher than those in control group (10% and 16% respectively); the AL risk for persons with Ile/Val + Val/Val was 3.260-fold (95%CI = 1.527 - 5.236) of persons with Ile/Ile. The further stratified analysis showed the frequency of Ile/Val + Val/Val in AML group was higher than that in control group (55% vs 16%, p < 0.05); the AML risk for persons with Ile/Val + Val/Val was 2.214-fold (95% CI = 1.009-3.260) as persons with Ile/Ile. The frequencies of C2 allele (16.7%) and C1C2/C2C2 of CYP2E1 gene (30%) in AL group seemed higher than those in control groups (13.9% and 26%), but the difference between them was not statistical significant (p > 0.05). The further stratified analysis showed that C1C2/C2C2 of CYP2E1 gene occurred more frequently in AML group (36%) than that in control group (32%), but there was no statistical difference between them (p > 0.05). Combined genotype analysis showed that the AML risk for persons in combination of lle/Val + Val/Val of GSTP1 gene with C1C2 + C2C2 of CYP2E1 gene increased by 3.208-fold. It is concluded that the GSTP1 gene is related with susceptibility to AML, the AL risk for persons with lle/Val + Val/Val of GSTP1 gene decreased, while CYP2E1 gene is not related with susceptibility to AL, the AML risk for persons in combination of GSTP1 wildtype with CYP2E1 hybrid and mutant genotype can be further decreased.

[Association of CD38 gene polymorphism with pathogenesis of chronic myeloid leukemia].

This study was aimed to investigate the distribution of CD38 gene 184 locus allele frequency in chronic myeloid leukemia (CML) and its relation with genetic susceptibility of CML. 100 cases of CML were enrolled in patient group; 200 cases of nonhematologic diseases and nontumor diseases were enrolled in control group. The CD38 gene 184 locus polymorphism was detected by PCR-RFLP, the difference of genotypic frequencies in patient and control groups was analyzed by χ(2) test and Fisher exact probability test, the risk of genotype induced leukemia was expressed by odds ratio (OR) and 95% confidence interval (CI). The results showed that the distribution of CD38 gene 184 locus G/G, G/C, C/C genotypes was no significantly different between patients and control groups (p = 0.072). The wild type C/C was used as reference, the distribution of variant G/C genotype frequency in CML group was different statistically from control group (p = 0.032, OR value 0.517, 95%CI 0.283 - 0.947); the C allele frequency was used as reference, the G allele frequency in CML group was higher than that in control group (p = 0.028, OR value 0.597, 95%CI 0.377 - 0.94). It is concluded that the CD38 gene 184 locus G allele may be an protective gene against CML, and reduce the risk of CML relapse.