TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes.
TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next-generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases.
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Labex Inflamex, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.|Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Gregory
G
Lazarian
Department of Internal Medicine III, Ulm University, Ulm, Germany.
Eugen
E
Tausch
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Virginie
V
Eclache
Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Amel
A
Sebaa
Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Vincent
V
Bianchi
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Labex Inflamex, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.|Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Remi
R
Letestu
Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Jean-Francois
JF
Collon
Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Valerie
V
Lefebvre
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Labex Inflamex, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.
Laura
L
Gardano
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Labex Inflamex, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.
Nadine
N
Varin-Blank
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska (CCK) R8:04, Stockholm SE-171 76, Sweden; Sorbonne Universités, UPMC Univ Paris 06, Paris, F-75005, France.|INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Thierry
T
Soussi
Department of Internal Medicine III, Ulm University, Ulm, Germany.
Stephen
S
Stilgenbauer
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Labex Inflamex, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.|Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Florence
F
Cymbalista
U978 Institut National De La Santé Et De La Recherche Médicale, Bobigny, France.|Labex Inflamex, Université Paris 13, Sorbonne Paris Cité, Bobigny, France.|Hôpital Avicenne, Assistance Publique-Hôpitaux De Paris, Bobigny, Service D'Hématologie Biologique, France.
Fanny
F
Baran-Marszak
D018450:Disease Progression; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008137:Longitudinal Studies; D009154:Mutation; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
CLL; TP53; clonal evolution