title: LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Kristensen
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kristensen
authors.affiliation: Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Royo
authors.affiliation: Department of Hematology, Hospital of Southern Jutland, Aabenraa, Denmark.
authors.forename: Mikael
authors.initials: M
authors.lastname: Frederiksen
authors.affiliation: Department of Hematology, Hospital of Southwestern Jutland, Esbjerg, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Mourits-Andersen
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D051881:Receptor, Notch1 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D051881:Receptor, Notch1; D016159:Tumor Suppressor Protein p53; D051746:ZAP-70 Protein-Tyrosine Kinase; D008071:Lipoprotein Lipase
keywords: LPL gene expression; NOTCH1 mutations; chronic lymphocytic leukemia; prognosis