Prognostic impact of NOTCH1 and MYD88 mutations in chronic lymphocytic leukemia patients

Autor:	Krzysztof Giannopoulos, Paulina Wlasiuk, Elżbieta Starosławska, Ewelina Zakrzewska, Joanna Purkot, Agnieszka Karczmarczyk
Rok vydání:	2019
Předmět:	Oncology Mutation medicine.medical_specialty business.industry Chronic lymphocytic leukemia hemic and immune systems Disease CD38 medicine.disease_cause medicine.disease Exon Leukemia medicine.anatomical_structure hemic and lymphatic diseases Internal medicine medicine Bone marrow business Gene
Zdroj:	Journal of Transfusion Medicine. 12:101-108
ISSN:	2080-1505 1689-6017
Popis:	Background. Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults with highly heterogeneous clinical course of the disease. Currently available prognostic factors are not fully efficient in predicting the course of CLL. New molecular mutations such as NOTCH1 and MYD88 could partly explain the CLL heterogeneity and help in identifying clinically relevant groups of patients. Material and methods. NOTCH1 c.7544_7545delCT (n = 200) in PEST domain (exon 34) and MYD88 L265P (n = 60) mutations was investigated by amplification refractory mutation system (ARMS). Expression of MYD88 in CLL was assessed in peripheral blood (PB) (n = 60) and bone marrow (BM) (n = 92) of CLL patients and 25 healthy volunteers (HVs) using qRT-PCR. Results. NOTCH1 mutation occurred in 18/200 (9.0%) CLL patients. Patients harboring NOTCH1 mutations prevalently belonged to aggressive cases, i.e. cases with an unmutated IGVH gene status, expression of CD38 and ZAP-70. MYD88 mutation occurred in 2/60 (3.3%) CLL patients. MYD88 mutations were strikingly enriched among patients expressing mutated IGVH genes. Our study demonstrated significantly higher PB MYD88 expression than in HVs and relevantly higher PB MYD88 expression in comparison with BM (respectively p < 0.0001 and p = 0.0015). There was no correlation between MYD88 expression in PB and BM and expression of ZAP-70, CD38 and IGVH mutational status. Conclusions. NOTCH1 mutations are more frequently detected in cases with unfavorable biological markers and seem to be independent predictive markers for worse outcome in CLL patients. Further collaborative studies in CLL are obligate to study the prognostic and predictive relevance of MYD88 mutations and expression.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::385a6c9067359fc3af26bdf17e5c8bc5 https://doi.org/10.5603/jtm.2019.0006 Zobrazit plný text záznamu