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The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness

The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness
The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness
Del17p13 predicts poor outcome and chemorefractoriness in chronic lymphocytic leukemia (CLL). Conversely, it is unknown whether TP53 mutations carry any prognostic value independent of del17p13. We tested the independent prognostic value of TP53 mutations in CLL.

Experimental Design: The study was based on a consecutive series of 308 CLL. DNA sequencing of TP53 exons 2 to 10 and del17p13 interphase fluorescence in situ hybridization were done at CLL diagnosis. Study end points were survival and chemorefractoriness.

Results: At diagnosis, TP53 mutations (n = 32) occurred in 31 of 308 (10.0%) patients. Of all CLL showing TP53 disruption by either mutation and/or deletion (n = 44), 10 cases (22.7%) showed TP53 mutations in the absence of del17p13. Multivariate analysis selected TP53 mutations (hazard ratio, 3.20; P = 0.002) as an independent predictor of overall survival after adjustment for del17p13. Also, multivariate analysis selected TP53 mutations (hazard ratio, 3.97; P < 0.001) as an independent predictor of chemorefractoriness after adjustment for del17p13. Compared with cases without TP53 alterations, CLL harboring any type of TP53 disruption (mutation only, del17p13 only, or both mutation and del17p13) uniformly displayed a high prevalence of unfavorable prognosticators and poor outcome. Analysis of sequential CLL samples showed the acquisition of new or additional TP53 alterations at the time of chemorefractoriness.

Conclusions: These data show that (a) TP53 mutations are an independent predictor of short survival and chemorefractoriness, and (b) that CLL presenting with TP53 mutations without del17p13 fare as poorly as CLL carrying del17p13. Because CLL harboring TP53 mutations without del17p13 are currently not recognized by conventional diagnostic strategies, these results may be relevant for a comprehensive prognostic characterization of CLL.
chronic lymphocytic leukemia, TP53 mutations, 17p deletion, chemorefractoriness, prognosis
1078-0432
995-1004
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Cerri, Michaela
59be0e0f-7336-4df6-ab05-52815a51a635
Deambrogi, Clara
c7d10651-681c-41b9-97b6-bf68f3c1243d
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Cresta, Stefania
bc5c756c-4800-4ca2-a825-888a607ace3d
Rasi, Silvia
13639ced-c17f-4350-87e4-fb670cee592b
De Paoli, Lorenzo
9390755d-1a39-47e9-bc54-69f9fe914248
Spina, Valeria
bb72602d-3d56-424f-b169-47377aef1d10
Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Capello, Daniela
f4d381f4-aaa6-47ae-bebf-53b0aed65055
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Cerri, Michaela
59be0e0f-7336-4df6-ab05-52815a51a635
Deambrogi, Clara
c7d10651-681c-41b9-97b6-bf68f3c1243d
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Cresta, Stefania
bc5c756c-4800-4ca2-a825-888a607ace3d
Rasi, Silvia
13639ced-c17f-4350-87e4-fb670cee592b
De Paoli, Lorenzo
9390755d-1a39-47e9-bc54-69f9fe914248
Spina, Valeria
bb72602d-3d56-424f-b169-47377aef1d10
Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Capello, Daniela
f4d381f4-aaa6-47ae-bebf-53b0aed65055
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a

Rossi, Davide, Cerri, Michaela, Deambrogi, Clara, Sozzi, Elisa, Cresta, Stefania, Rasi, Silvia, De Paoli, Lorenzo, Spina, Valeria, Gattei, Valter, Capello, Daniela, Forconi, Francesco, Lauria, Francesco and Gaidano, Gianluca (2009) The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clinical Cancer Research, 15 (3), 995-1004. (doi:10.1158/1078-0432.CCR-08-1630). (PMID:19188171)

Record type: Article

Abstract

Del17p13 predicts poor outcome and chemorefractoriness in chronic lymphocytic leukemia (CLL). Conversely, it is unknown whether TP53 mutations carry any prognostic value independent of del17p13. We tested the independent prognostic value of TP53 mutations in CLL.

Experimental Design: The study was based on a consecutive series of 308 CLL. DNA sequencing of TP53 exons 2 to 10 and del17p13 interphase fluorescence in situ hybridization were done at CLL diagnosis. Study end points were survival and chemorefractoriness.

Results: At diagnosis, TP53 mutations (n = 32) occurred in 31 of 308 (10.0%) patients. Of all CLL showing TP53 disruption by either mutation and/or deletion (n = 44), 10 cases (22.7%) showed TP53 mutations in the absence of del17p13. Multivariate analysis selected TP53 mutations (hazard ratio, 3.20; P = 0.002) as an independent predictor of overall survival after adjustment for del17p13. Also, multivariate analysis selected TP53 mutations (hazard ratio, 3.97; P < 0.001) as an independent predictor of chemorefractoriness after adjustment for del17p13. Compared with cases without TP53 alterations, CLL harboring any type of TP53 disruption (mutation only, del17p13 only, or both mutation and del17p13) uniformly displayed a high prevalence of unfavorable prognosticators and poor outcome. Analysis of sequential CLL samples showed the acquisition of new or additional TP53 alterations at the time of chemorefractoriness.

Conclusions: These data show that (a) TP53 mutations are an independent predictor of short survival and chemorefractoriness, and (b) that CLL presenting with TP53 mutations without del17p13 fare as poorly as CLL carrying del17p13. Because CLL harboring TP53 mutations without del17p13 are currently not recognized by conventional diagnostic strategies, these results may be relevant for a comprehensive prognostic characterization of CLL.

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More information

Published date: 1 February 2009
Keywords: chronic lymphocytic leukemia, TP53 mutations, 17p deletion, chemorefractoriness, prognosis
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358156
URI: http://eprints.soton.ac.uk/id/eprint/358156
ISSN: 1078-0432
PURE UUID: 885e593b-e6dd-4302-be19-070ebf40fc5a
ORCID for Francesco Forconi: ORCID iD orcid.org/0000-0002-2211-1831

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Date deposited: 08 Oct 2013 13:18
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Davide Rossi
Author: Michaela Cerri
Author: Clara Deambrogi
Author: Elisa Sozzi
Author: Stefania Cresta
Author: Silvia Rasi
Author: Lorenzo De Paoli
Author: Valeria Spina
Author: Valter Gattei
Author: Daniela Capello
Author: Francesco Lauria
Author: Gianluca Gaidano

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