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Leukemia & Lymphoma Volume 58, 2017 - Issue 1
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Original Articles: Clinical

COBLL1, LPL and ZAP70 expression defines prognostic subgroups of chronic lymphocytic leukemia patients with high accuracy and correlates with IGHV mutational status

Hana PlesingerovaCenter of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic; ;Department of Internal Medicine – Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic;
,
Zuzana LibrovaGENERI BIOTECH s.r.o, Hradec Kralove, Czech Republic;
,
Karla PlevovaCenter of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic; ;Department of Internal Medicine – Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic;
,
Antonin LibraGENERI BIOTECH s.r.o, Hradec Kralove, Czech Republic;
,
Boris TichyCenter of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic;
,
Hana Skuhrova FrancovaDepartment of Internal Medicine – Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic;
,
Filip Vrbacky4th Department of Internal Medicine – Hematology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove and Charles University, Hradec Kralove, Czech Republic;
,
Lukas Smolej4th Department of Internal Medicine – Hematology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove and Charles University, Hradec Kralove, Czech Republic;
,
Jiri MayerCenter of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic; ;Department of Internal Medicine – Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic;
,
Vitezslav BryjaDepartment of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic; ;Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
,
Michael DoubekCenter of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic; ;Department of Internal Medicine – Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic;
&
Sarka PospisilovaCenter of Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic; ;Department of Internal Medicine – Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic; Correspondence[email protected]
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Pages 70-79 | Received 08 Nov 2015, Accepted 13 Apr 2016, Published online: 17 May 2016
 
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Abstract

The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Patients with unmutated IGHV (U-CLL) usually progress rapidly, whereas patients with mutated IGHV (M-CLL) have a more indolent disease. The expression of several genes correlates closely with the IGHV mutational status and could be used to assess prognosis in CLL. We analyzed the prognostic relevance of COBLL1, LPL, and ZAP70 gene expression, which correlated with IGHV mutational status (p < 0.0001), in 117 CLL patients and established a prognostic parameter dividing the tested cohort according to the disease aggressiveness. Our prognostic parameter was validated on an independent cohort of 161 CLL patients and achieved a high accuracy (94%). Patients divided according to the prognostic parameter differ in overall survival and time to first treatment (p < 0.0001, HR  = 2.300/5.970, 95% CI: 1.587–3.450/4.621–15.86). Our approach provides a reliable alternative method to prognosis assessment via IGHV mutational status analysis.

Acknowledgements

This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic [CEITEC 2020/LQ1601], Technology Agency of the Czech Republic [TACR TE02000058], Masaryk University [MUNI/A/1028/2015], Czech Health Research Council [AZV MZ ČR 15-29793A, AZV MZ ČR 15-30015A], Ministry of Industry and Trade of the Czech Republic [MPO FR-TI2/254] and by the Czech Leukemia Study Group – for Life.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.180690.

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