TP53 Mutations Suggests Early Treatment Necessary

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The detection of TP53 mutations in chronic lymphocytic leukemia

independently predicts rapid disease progression and is highly

correlated with a complex aberrant karyotype

Leukemia, 10/16/08

Dicker F et al. †" In chronic lymphocytic leukemia (CLL) presence of

TP53 mutations is an independent predictor of rapid disease progression

Methods

* Study of whether TP53 mutation on the remaining allele

contributes to the poor prognosis in CLL or whether TP53 mutation

alone may be an adverse prognostic factor

* Review of TP53 mutations in 193 CLL pts

* Analysis by denaturing high performance liquid chromatography in

combination with direct DNA sequencing and a TP53 re-sequencing

research microarray

* Mutations correlated to chromosomal aberrations defined by

interphase fluorescent in situ hybridization and chromosome banding

analyses and to pt clinical course

Results

* TP53 mutations in 13.5% (26 of 193) of samples; incidence of del

(17p): 9.3% (18 of 193)

* TP53 mutations significantly associated with del (17p) and

complex cytogenetic abnormalities

* Of 147 pts with available clinical data, time to treatment

significantly decreased for pts with TP53 vs without TP53 aberration

* Median time to treatment: short in the 6 pts with isolated TP53

mutation (2 mo) and in the 14 pts with del (17p) (21.3 mo) vs the 127

pts without TP53 aberration (64.9 mo)

* In multivariate regression analysis, VH status, TP53

mutations and isolated TP53 mutations independently predicted rapid

disease progression