Specific p53 mutations do not impact results of alemtuzumab
therapy among patients with chronic lymphocytic leukemia

J 2012

Specific p53 mutations do not impact results of alemtuzumab therapy among patients with chronic lymphocytic leukemia

DOUBEK, Michael, Martin TRBUŠEK, Jitka MALČÍKOVÁ, Yvona BRYCHTOVÁ, Jana ŠMARDOVÁ et. al.

Basic information

Original name

Specific p53 mutations do not impact results of alemtuzumab therapy among patients with chronic lymphocytic leukemia

Authors

DOUBEK, Michael (203 Czech Republic, guarantor, belonging to the institution), Martin TRBUŠEK (203 Czech Republic, belonging to the institution), Jitka MALČÍKOVÁ (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Jana ŠMARDOVÁ (203 Czech Republic, belonging to the institution), Jana LOCHMANOVÁ (203 Czech Republic, belonging to the institution), Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Hana FRANCOVÁ (203 Czech Republic, belonging to the institution), Marek MRÁZ (203 Czech Republic, belonging to the institution), Boris TICHÝ (203 Czech Republic, belonging to the institution), Ludmila ŠEBEJOVÁ (203 Czech Republic, belonging to the institution), Veronika NAVRKALOVÁ (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Petr KUGLÍK (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution)

Edition

Leukemia & Lymphoma, LONDON, INFORMA HEALTHCARE, 2012, 1042-8194

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.301

RIV identification code

RIV/00216224:14740/12:00062071

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3109/10428194.2012.658794

UT WoS

000307301500031

Keywords in English

chronic lymphocytic leukemia; p53 mutation; alemtuzumab

Abstract

V originále

A poor prognosis in chronic lymphocytic leukemia (CLL) is associated particularly with the presence of del(17p) affecting tumor suppressor gene TP53. This deletion is in almost all cases of progressive leukemia accompanied by a mutation in the other TP53 allele, and in a smaller proportion of patients the TP53 mutation occurs also independently of del(17p). Recently, we demonstrated that patients with CLL harboring a missense mutation located in the p53 DNA-binding motifs (DBMs) (structurally well-defined parts of the DNA-binding domain) manifested a clearly shorter median survival in comparison with those having a missense mutation outside DBMs or a non-missense alteration. However, a limitation of this study resulted from the unpredictable survival impact of diverse therapy given to patients with p53 mutations. Th e therapeutic approach currently taken for patients with CLL with loss and/or mutation of TP53 relies mostly on the use of agents which do not act through DNA damage followed by apoptosis induction. Th e success of this approach has been documented for the monoclonal antibody alemtuzumab. Monotherapy with alemtuzumab is now being recommended as first-line therapy for patients with CLL with del(17p); however, many unresolved questions need to be addressed. For example, it is unclear whether the type of p53 mutation infl uences the outcome of alemtuzumab therapy.

Citovat

DOUBEK, Michael, Martin TRBUŠEK, Jitka MALČÍKOVÁ, Yvona BRYCHTOVÁ, Jana ŠMARDOVÁ, Jana LOCHMANOVÁ, Anna PANOVSKÁ, Hana FRANCOVÁ, Marek MRÁZ, Boris TICHÝ, Ludmila ŠEBEJOVÁ, Veronika NAVRKALOVÁ, Karla PLEVOVÁ, Petr KUGLÍK, Jiří MAYER and Šárka POSPÍŠILOVÁ. Specific p53 mutations do not impact results of alemtuzumab therapy among patients with chronic lymphocytic leukemia. Leukemia & Lymphoma. LONDON: INFORMA HEALTHCARE, 2012, vol. 53, No 9, p. 1817-1819. ISSN 1042-8194. Available from: https://dx.doi.org/10.3109/10428194.2012.658794.

@article{1075198,
   author = {Doubek, Michael and Trbušek, Martin and Malčíková, Jitka and Brychtová, Yvona and Šmardová, Jana and Lochmanová, Jana and Panovská, Anna and Francová, Hana and Mráz, Marek and Tichý, Boris and Šebejová, Ludmila and Navrkalová, Veronika and Plevová, Karla and Kuglík, Petr and Mayer, Jiří and Pospíšilová, Šárka},
   article_location = {LONDON},
   article_number = {9},
   doi = {http://dx.doi.org/10.3109/10428194.2012.658794},
   keywords = {chronic lymphocytic leukemia; p53 mutation; alemtuzumab},
   language = {eng},
   issn = {1042-8194},
   journal = {Leukemia & Lymphoma},
   title = {Specific p53 mutations do not impact results of alemtuzumab therapy among patients with chronic lymphocytic leukemia},
   url = {http://informahealthcare.com/doi/abs/10.3109/10428194.2012.658794},
   volume = {53},
   year = {2012}
}

TY  - JOUR
ID  - 1075198
AU  - Doubek, Michael - Trbušek, Martin - Malčíková, Jitka - Brychtová, Yvona - Šmardová, Jana - Lochmanová, Jana - Panovská, Anna - Francová, Hana - Mráz, Marek - Tichý, Boris - Šebejová, Ludmila - Navrkalová, Veronika - Plevová, Karla - Kuglík, Petr - Mayer, Jiří - Pospíšilová, Šárka
PY  - 2012
TI  - Specific p53 mutations do not impact results of alemtuzumab therapy among patients with chronic lymphocytic leukemia
JF  - Leukemia & Lymphoma
VL  - 53
IS  - 9
SP  - 1817-1819
EP  - 1817-1819
PB  - INFORMA HEALTHCARE
SN  - 10428194
KW  - chronic lymphocytic leukemia
KW  - p53 mutation
KW  - alemtuzumab
UR  - http://informahealthcare.com/doi/abs/10.3109/10428194.2012.658794
L2  - http://informahealthcare.com/doi/abs/10.3109/10428194.2012.658794
N2  - A poor prognosis in chronic lymphocytic leukemia (CLL) is associated particularly with the presence of del(17p) affecting tumor suppressor gene TP53. This deletion is in almost all cases of progressive leukemia accompanied by a mutation in the other TP53 allele, and in a smaller proportion of patients the TP53 mutation occurs also independently of del(17p). Recently, we demonstrated that patients with CLL harboring a missense mutation located in the p53 DNA-binding motifs (DBMs) (structurally well-defined parts of the DNA-binding domain) manifested a clearly shorter median survival in comparison with those having a missense mutation outside DBMs or a non-missense alteration. However, a limitation of this study resulted from the unpredictable survival impact of diverse therapy given to patients with p53 mutations. Th e therapeutic approach currently taken for patients with CLL with loss and/or mutation of TP53 relies mostly on the use of agents which do not act through DNA damage followed by apoptosis induction. Th e success of this approach has been documented for the monoclonal antibody alemtuzumab. Monotherapy with alemtuzumab is now being recommended as first-line therapy for patients with CLL with del(17p); however, many unresolved questions need to be addressed. For example, it is unclear whether the type of p53 mutation infl uences the outcome of alemtuzumab therapy.
ER  -

DOUBEK, Michael, Martin TRBUŠEK, Jitka MALČÍKOVÁ, Yvona BRYCHTOVÁ, Jana ŠMARDOVÁ, Jana LOCHMANOVÁ, Anna PANOVSKÁ, Hana FRANCOVÁ, Marek MRÁZ, Boris TICHÝ, Ludmila ŠEBEJOVÁ, Veronika NAVRKALOVÁ, Karla PLEVOVÁ, Petr KUGLÍK, Jiří MAYER and Šárka POSPÍŠILOVÁ. Specific p53 mutations do not impact results of alemtuzumab therapy among patients with chronic lymphocytic leukemia. \textit{Leukemia \&{} Lymphoma}. LONDON: INFORMA HEALTHCARE, 2012, vol.~53, No~9, p.~1817-1819. ISSN~1042-8194. Available from: https://dx.doi.org/10.3109/10428194.2012.658794.

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