The TP53 mutational landscape in CLL is very complex

[Jm954]

December 8, 2019

Interesting poster shedding a bit more light on the complexity of TP53 mutations and its independence from 17p deletion.

"TP53 aberrations, including somatic mutations of TP53 gene or 17p deletion leading to the loss of the TP53 locus, are a major predictive factor of resistance to fludarabin based chemotherapy in chronic lymphocytic leukemia (CLL) and remain an adverse prognostic factor in the chemofree era.

Of the 343 patients, 113 (33%) were poly-mutated and harbored more than one pathogenic TP53 variants (2 to 11 variants per patient): 57 (16,7 %) had 2 variants, 32 (9,3%) had 3, 10 had 4 (3%) and 14 patients (4%) had 5 to 11 variants. These variants were distributed in different alleles supporting an important intra-tumoral heterogeneity and a strong selection for TP53 loss of function during tumor progression in these patients.

Multiclonal mutations were predominantly found in previously treated patients (41% treated versus 10 % untreated) but whether all these variants preceded treatment and were further selected is currently unknown. They observed that 71.5 % of patients were IGHV unmutated and multiclonal mutations were surprisingly more frequent in mutated IGHV cases than in unmutated ones.

Only 50% of cases carried a 17p deletion, highlighting again the importance of testing for TP53 mutations in addition to FISH analysis. Presence or absence of 17p deletion was unrelated to the number of TP53 mutations."

More detail here: ash.confex.com/ash/2019/web...

Jackie

[Hidden]

since i have both -can't do anything about it.

[Justasheet1 in reply to Hidden]

IVFN,

Sorry to hear that. Aside from knowing, does it affect how your doctor controls your disease? I would suspect it doesn’t other than there being a Zero percent chance of chemo.

Jeff

[Hidden in reply to Justasheet1]

i have b-pll. all b-pll known have del 17 or tp53 or combination of both. Yes no chemo-thank god the p17 tp53 were developed for chemo not novel drugs. We are treated as high risk cll