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.

Základní údaje

Originální název

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

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 2.301

Kód RIV

RIV/00216224:14740/12:00062071

Organizační jednotka

Středoevropský technologický institut

UT WoS

000307301500031

Klíčová slova anglicky

chronic lymphocytic leukemia; p53 mutation; alemtuzumab

Štítky

Příznaky

Mezinárodní význam
Změněno: 12. 4. 2013 10:12, Olga Křížová

Anotace

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.