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Expression of B7-H6 in chronic myeloid leukemia and its clinical significance.

ABSTRACT: OBJECTIVE:To examine the expression level of B7-H6 in chronic myeloid leukemia (CML) patients and to explore its clinical significance. METHODS:Two hundred twenty-eight CML patients were included and peripheral blood (PB) and bone marrow (BM) mononuclear cells were collected for B7-H6 mRNA expression analyses by quantitative real time polymerase chain reaction (PCR). RESULTS:The expression of B7-H6 mRNA was successfully detected in all PB and BM samples. According to the clinical characteristics of CML patients, no difference was found in the B7-H6 level of PBMCs. However, a significantly decreased B7-H6 level was noted in BM samples from CML with BCR-ABL1/ABL > 0.1% (10 copies of BCR-ABL1/10000 copies of ABL) compared to ≤ 0.1% (P < 0.0001), and a negative correlation was found between the expression level of B7-H6 in BM and the number of BCR-ABL1/ABL transcripts (r = -0.26, P = 0.0057). A significant difference in PFS was observed between patients with high expression level of B7-H6 and low expression level in BM (χ2 = 12.53, P = 0.0004). CONCLUSION:The expression of the B7-H6 gene in CML is correlated with BCR-ABL1 copy number and responsiveness to treatment, and monitoring of B7-H6 expression may be used to predict CML prognosis, progression, and treatment efficacy evaluation.

SUBMITTER: Cao Y

PROVIDER: S-EPMC6945099 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Expression of B7-H6 in chronic myeloid leukemia and its clinical significance.

Cao Yanglin Y Huo Li L Zhou Ling L Yang Jianfeng J Weng Zhen Z Yang Xiaofei X Cen Jiannong J He Yang Y

International journal of clinical and experimental pathology 20190201 2

<h4>Objective</h4>To examine the expression level of B7-H6 in chronic myeloid leukemia (CML) patients and to explore its clinical significance.<h4>Methods</h4>Two hundred twenty-eight CML patients were included and peripheral blood (PB) and bone marrow (BM) mononuclear cells were collected for B7-H6 mRNA expression analyses by quantitative real time polymerase chain reaction (PCR).<h4>Results</h4>The expression of B7-H6 mRNA was successfully detected in all PB and BM samples. According to the cl ...[more]

PMID: 31933861

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Project description:BackgroundThe relationship between ferroptosis and the progression and treatment of hematological tumors has been extensively studied, although its precise association with chronic myeloid leukemia (CML) remains uncertain.MethodsMulti-transcriptome sequencing data were utilized to analyze the ferroptosis level of CML samples and its correlation with the tumor microenvironment, disease progression, and treatment response. Machine learning algorithms were employed to identify diagnostic ferroptosis-related genes (FRGs). The consensus clustering algorithm was applied to identify ferroptosis-related molecular subtypes. Clinical samples were collected for sequencing to validate the results obtained from bioinformatics analysis. Cell experiments were conducted to investigate the therapeutic efficacy of induced ferroptosis in drug-resistant CML.ResultsFerroptosis scores were significantly lower in samples from patients with CML compared to normal samples, and these scores further decreased with disease progression and non-response to treatment. Most FRGs were downregulated in CML samples. A high ferroptosis score was also associated with greater immunosuppression and increased activity of metabolic pathways. Through support vector machine recursive feature elimination (SVM-RFE), least absolute shrinkage selection operator (LASSO), and random forest (RF) algorithms, we identified five FRGs (ACSL6, SLC11A2, HMOX1, SLC38A1, AKR1C3) that have high diagnostic value. The clinical diagnostic value of these five FRGs and their effectiveness in differentiating CML from other hematological malignancies were validated using additional validation cohorts and our real-world cohort. There are significant differences in immune landscape, chemosensitivity, and immunotherapy responsiveness between the two ferroptosis-related molecular subtypes. By conducting cellular experiments, we confirmed that CML-resistant cells are more sensitive to induction of ferroptosis and can enhance the sensitivity of imatinib treatment.ConclusionOur study unveils the molecular signature of ferroptosis in samples from patients with CML. FRG identified by a variety of machine learning algorithms has reliable clinical diagnostic value. Furthermore, the characterization of different ferroptosis-related molecular subtypes provides valuable insights into individual patient characteristics and can guide clinical treatment strategies. Targeting and inducing ferroptosis holds great promise as a therapeutic approach for drug-resistant CML.

Dataset Information

Expression of B7-H6 in chronic myeloid leukemia and its clinical significance.

Publications

Expression of B7-H6 in chronic myeloid leukemia and its clinical significance.

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