LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations
| Autor: | Louise Kristensen, Thomas Kielsgaard Kristensen, Niels Abildgaard, Michael Boe Møller, Elias Campo, Torben Mourits-Andersen, Mikael Frederiksen, Cristina Royo |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Somatic cell Chronic lymphocytic leukemia Disease Bioinformatics medicine.disease_cause Exon 0302 clinical medicine hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols Medicine Immunoglobulin Heavy Chains/genetics Receptor Notch1 Lpl gene NOTCH1 mutations Aged 80 and over Mutation ZAP-70 Protein-Tyrosine Kinase Gene Expression Regulation Leukemic digestive oral and skin physiology Hematology General Medicine Middle Aged Prognosis LPL gene expression 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Tumor Suppressor Protein p53/genetics Female Immunoglobulin Heavy Chains ZAP-70 Protein-Tyrosine Kinase/genetics Leukemia Lymphocytic Chronic B-Cell/diagnosis 03 medical and health sciences Humans Lipoprotein Lipase/genetics Gene Proportional Hazards Models Aged Neoplasm Staging Receptor Notch1/genetics Proportional hazards model business.industry nutritional and metabolic diseases medicine.disease Leukemia Lymphocytic Chronic B-Cell Lipoprotein Lipase Cancer research chronic lymphocytic leukemia Antineoplastic Combined Chemotherapy Protocols/therapeutic use Tumor Suppressor Protein p53 business 030215 immunology |
| Zdroj: | Kristensen, L, Kielsgaard Kristensen, T, Abildgaard, N, Royo, C, Frederiksen, M, Mourits-Andersen, H T, Campo, E & Møller, M B 2016, ' LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations ', European Journal of Haematology, vol. 97, no. 2, pp. 175-182 . https://doi.org/10.1111/ejh.12700 |
| DOI: | 10.1111/ejh.12700 |
| Popis: | Introduction Chronic lymphocytic leukemia is a heterogeneous yet incurable disease. Whole-genome and whole-exome sequencing studies have revealed recurrently occurring somatic mutations in some genes. Several other prognostic markers have previously been tested for their prognostic value in CLL. LPL is among these markers. Aim To evaluate LPL gene expression together with the well-established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations. Methods On 149 patients, LPL gene expression was analyzed by real-time RT-PCR. Exon 34 of NOTCH1 was PCR-amplified and directly sequenced. Results LPL gene expression could be measured as a categorical variable (LPL+/LPL-) and was associated with time to treatment (P < 0.001) and overall survival (P = 0.007). In patients otherwise classified as having a good prognosis according to established and new prognostic markers, 3 of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (P = 0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (P = 0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild-type NOTCH1. Conclusions NOTCH1 mutations are tightly associated with LPL gene expression. LPL expression is independently associated with poor outcome in CLL and can be measured as a categorical variable. |
| Databáze: | OpenAIRE |
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