Louise Kristensen1, Thomas Kristensen1, Niels Abildgaard2, Cristina Royo3, Mikael Frederiksen4, Torben Mourits-Andersen5, Elias Campo3, Michael Boe Møller1. 1. Department of Pathology, Odense University Hospital, Odense, Denmark. 2. Department of Hematology, Odense University Hospital, Odense, Denmark. 3. Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain. 4. Department of Hematology, Hospital of Southern Jutland, Aabenraa, Denmark. 5. Department of Hematology, Hospital of Southwestern Jutland, Esbjerg, Denmark.
Abstract
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.
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.
Authors: Lisa M Butler; Ylenia Perone; Jonas Dehairs; Leslie E Lupien; Vincent de Laat; Ali Talebi; Massimo Loda; William B Kinlaw; Johannes V Swinnen Journal: Adv Drug Deliv Rev Date: 2020-07-23 Impact factor: 15.470
Authors: Leslie E Lupien; Katarzyna Bloch; Jonas Dehairs; Nicole A Traphagen; William W Feng; Wilson L Davis; Thea Dennis; Johannes V Swinnen; Wendy A Wells; Nicole C Smits; Nancy B Kuemmerle; Todd W Miller; William B Kinlaw Journal: J Lipid Res Date: 2019-12-05 Impact factor: 5.922
Authors: Zoltán Mátrai; Hajnalka Andrikovics; Anikó Szilvási; András Bors; András Kozma; Emma Ádám; Gabriella Halm; Éva Karászi; Attila Tordai; Tamás Masszi Journal: Pathol Oncol Res Date: 2016-10-18 Impact factor: 3.201
Authors: Dan Cao; Xinhua Song; Li Che; Xiaolei Li; Maria G Pilo; Gianpaolo Vidili; Alberto Porcu; Antonio Solinas; Antonio Cigliano; Giovanni M Pes; Silvia Ribback; Frank Dombrowski; Xin Chen; Lei Li; Diego F Calvisi Journal: Liver Int Date: 2016-07-06 Impact factor: 5.828
Authors: Yixin Zou; Lei Fan; Yi Xia; Yi Miao; Wei Wu; Lei Cao; Jiazhu Wu; Huayuan Zhu; Chun Qiao; Li Wang; Wei Xu; Jianyong Li Journal: Cancer Med Date: 2018-03-23 Impact factor: 4.452
Authors: Dianna Hussmann; Anna Starnawska; Louise Kristensen; Iben Daugaard; Astrid Thomsen; Tina E Kjeldsen; Christine Søholm Hansen; Jonas Bybjerg-Grauholm; Karina Dalsgaard Johansen; Maja Ludvigsen; Thomas Kristensen; Thomas Stauffer Larsen; Michael Boe Møller; Charlotte Guldborg Nyvold; Lise Lotte Hansen; Tomasz K Wojdacz Journal: Haematologica Date: 2022-04-01 Impact factor: 9.941