open access

Vol 12, No 3 (2019)
Research paper
Published online: 2019-11-28
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Prognostic impact of NOTCH1 and MYD88 mutations in chronic lymphocytic leukemia patients

Ewelina Zakrzewska, Agnieszka Karczmarczyk, Joanna Purkot, Paulina Własiuk, Krzysztof Giannopoulos, Elżbieta Starosławska
Journal of Transfusion Medicine 2019;12(3):92-100.

open access

Vol 12, No 3 (2019)
ORIGINAL PAPERS
Published online: 2019-11-28

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) is one of the most common type of leukemia in adults with highly heterogenous clinical course of the disease. Currently available prognostic factors are not fully efficient in predicting the course of CLL. New molecular mutations like 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 (ARMS) amplification refractory mutation system. Expression of MYD88 in CLL was assessed in (PB) peripheral blood (n=60) and (BM) bone marrow (n=92) CLL patients and 25 (HVs) healthy volunteers 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 occured 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 seems 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.

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) is one of the most common type of leukemia in adults with highly heterogenous clinical course of the disease. Currently available prognostic factors are not fully efficient in predicting the course of CLL. New molecular mutations like 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 (ARMS) amplification refractory mutation system. Expression of MYD88 in CLL was assessed in (PB) peripheral blood (n=60) and (BM) bone marrow (n=92) CLL patients and 25 (HVs) healthy volunteers 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 occured 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 seems 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.
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Keywords

chronic lymphocytic leukemia; NOTCH1; MYD88; prognostic factors; ARMS-PCR

About this article
Title

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

Journal

Journal of Transfusion Medicine

Issue

Vol 12, No 3 (2019)

Article type

Research paper

Pages

92-100

Published online

2019-11-28

Bibliographic record

Journal of Transfusion Medicine 2019;12(3):92-100.

Keywords

chronic lymphocytic leukemia
NOTCH1
MYD88
prognostic factors
ARMS-PCR

Authors

Ewelina Zakrzewska
Agnieszka Karczmarczyk
Joanna Purkot
Paulina Własiuk
Krzysztof Giannopoulos
Elżbieta Starosławska

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