Article

LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations

European Journal Of Haematology, Wiley, ISSN 1600-0609

Volume 97, 2, 2016

DOI:10.1111/ejh.12700, Dimensions: pub.1036449689, PMID: 26558352,

Affiliations

Organisations

  1. (1) Odense University Hospital, grid.7143.1, Southern Denmark Region
  2. (2) University of Barcelona, grid.5841.8
  3. (3) Hospital of Southern Jutland, grid.416811.b, Southern Denmark Region
  4. (4) Hospital of South West Jutland, grid.414576.5, Southern Denmark Region

Countries

Denmark

Spain

Continents

Europe

Description

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.

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University of Southern Denmark

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Times Cited: 12

Field Citation Ratio (FCR): 3.12

Relative Citation ratio (RCR): 0.68