The Landscape Of Genetic Mutations In Patients With Chronic Lymphocytic Leukemia And Complex Karyotype
Morressier, 2017
Online
unknown
Zugriff:
Context. Complex karyotype (CK) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). While mutations in TP53 have been associated with CK, overlap is not complete and the genetic landscape of patients with CLL and CK remains largely undescribed.Design. We performed targeted next generation sequencing with a SureSelect custom panel of 295 genes (Agilent Technologies, Santa Clara, CA) on bone marrow aspirate collected between March 2003 and October 2015 from 71 patients with CLL and CK, and compared them to a control group of 90 patients without CK, age and sex-matched.Results. In univariable analyses (UVA), CK was associated with Rai III-IV disease (61% vs 36%, p=0.002), beta-2 microglobulin (B2M) > 4 mg/L (67% vs 40%, p=0.001), del(17p) by FISH (33% vs 9%, p10% of patients) were TP53 (32%), SF3B1 (15.5%) and NOTCH1 (10%). When compared to the non-CK cohort, patients with CK showed a significantly higher prevalence of TP53 (32% vs 11%, p=0.001) and SETD2 mutations (6% vs 0%, p=0.04). On multivariable analysis (MVA), B2M >4 mg/L (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-5.3; p=0.02) and del(17p) by FISH (OR 3.6, 95% CI 1.2-10.4, p=0.02) were independently associated with CK.After a median follow-up of 17 months (range, 1-141 months), among the 71 patients with CLL and CK, 29 (41%) died, and median overall survival (OS) was 56 months (range, 1-141 months). Factors significantly associated with shorter OS in UVA were unmutated IGHV (32 months vs 132 months, p=0.02), mutated NOTCH1 (17 months vs 60 months, p=0.02) and mutated TP53 (32 months vs 62 months, p=0.05). In MVA, unmutated IGHV (hazard ratio [HR] 5.2, 95% CI 1.2-22.7; p=0.03) and mutated NOTCH1 (HR 5.8, 95% CI 1.6-20.4; p=0.007) maintained their association with shorter survival. Conclusions. This is the first study specifically dissecting the genomic landscape of patients with CLL and CK. Further investigation of the role of mutated SETD2 and mutated NOTCH1 may improve the management and treatment of this very high risk population.
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The Landscape Of Genetic Mutations In Patients With Chronic Lymphocytic Leukemia And Complex Karyotype
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Veröffentlichung: | Morressier, 2017 |
Medientyp: | unknown |
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