TP53 Gene 72 Arg/Pro (rs1042522) single nucleotide polymorphism increases the risk and the severity of chronic lymphocytic leukemia

Ounalli, Asma; Moumni, Imen; Mechaal, Amal; Chakroun, Aya; Barmat, Mbarka; Rhim, Rim El Elj; Menif, Samia; Safra, Ines

doi:10.3389/fonc.2023.1272876

Cited by 5 publications

(1 citation statement)

References 51 publications

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“…Additionally, TP53 rs2454206 has been extensively investigated as a germline predisposition factor for cancer. Despite conflicting data, this SNP may increase the risk of colorectal cancer (36), chronic lymphocytic leukemia (37), and acute myeloid leukemia with adverse molecular and cytogenetic risk (38).…”

Section: Discussionmentioning

confidence: 99%

Morphological, clinical, and molecular profiling of post-polycythemia vera accelerated/blast phase occurring with and without antecedent secondary myelofibrosis

Pelagatti,

Pozzi,

Cortellazzi

et al. 2024

Front. Hematol.

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IntroductionPolycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm (MPN) characterized by clonal erythrocytosis and an intrinsic risk of transformation into acute myeloid leukemia (AML), known as blast-phase (BP) disease, a condition typified by dismal prognosis. In PV, the evolution to BP generally occurs through an overt fibrotic progression, represented by the post-PV myelofibrotic (MF) stage. However, direct leukemic transformation from PV may also occur in up to ~50% of patients. In this study, we sought to shed light on the morphological, clinical, and molecular features that may differentiate BP arising from a direct transition from the PV stage (post-PV-BP) from those evolving through a diagnosis of post-PV myelofibrosis (post-PV-MF-BP). Methods and resultsWe retrospectively analyzed a cohort of post-PV-BP (n=5) and post-PV-MF-BP (n=5). We found that BP arising from PV directly displayed significantly lower leukocyte count (median 2.93 × 109/L, range: 2.30–39.40 vs. median 41.05 × 109/L, range: 5.46–58.01; P=0.03), and spleen diameter (14.0 cm, range: 11.5–20.0 vs. 25.5 cm, range: 18–26; P=0.03) as compared to those experiencing an overt fibrotic stage. The most striking differences emerged from bone marrow (BM) morphological analysis: all post-PV-BP were characterized by significantly higher cellularity (median 70%, range: 60%–98% vs. 28%, range: 2%–41%, P=0.0245), lower degree of fibrosis (fibrosis grade 1 vs. fibrosis grade 3 in all cases, P=0.008) and dysplastic features involving all three lineages, most prominently the erythroid and megakaryocytic compartment. Next-generation sequencing (NGS) analysis revealed that post-PV-BP cases were enriched in mutations located in genes involved in DNA methylation such as DNMT3A, IDH1/2, and TET2 (45% vs. 15%, P=0.038). DiscussionWith all the limits of the small number of patients for each cohort, our data suggest that BPs that arise directly from PV present a peculiar phenotype, consistent with the molecular signature of the disease, typified by mutations of genes occurring with a high frequency in Myelodysplastic Syndromes (MDS) and MDS/MPN. Further studies in larger cohorts are warranted to translate these observations into robust evidence that may advise therapeutic choices.

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Section: Discussionmentioning

confidence: 99%

Morphological, clinical, and molecular profiling of post-polycythemia vera accelerated/blast phase occurring with and without antecedent secondary myelofibrosis

Pelagatti,

Pozzi,

Cortellazzi

et al. 2024

Front. Hematol.

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Genetic variability profiling of the p53 signaling pathway in chronic lymphocytic leukemia. Individual and combined analysis of TP53, MDM2 and NQO1 gene variants

Fontecha,

Anadón,

Mercado Guzmán

et al. 2024

Ann Hematol

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Single Nucleotide Polymorphism-based Identification of Bacterial Artificial Chromosome-mediated Homologous Recombination

Chung

2024

Front. Biosci. (Landmark Ed)

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Bacterial Artificial chromosome (BAC) recombineering is a powerful genetic manipulation tool for the efficient development of recombinant genetic resources. Long homology arms of more than 150 kb composed of BAC constructs not only substantially enhance genetic recombination events, but also provide a variety of single nucleotide polymorphisms (SNPs) that are useful markers for accurately docking BAC constructs at target sites. Even if the BAC construct is homologous to the sequences of the target region, different variations may be distributed between various SNPs within the region and those within the BAC construct. Once the BAC construct carrying these variations was precisely replaced in the target region, the SNP profiles within the target genomic locus were directly replaced with those in the BAC. This alteration in SNP profiles ensured that the BAC construct accurately targeted the designated site. In this study, we introduced restriction fragment length polymorphism or single-strand conformation polymorphism analyses to validate and evaluate BAC recombination based on changes in SNP patterns. These methods provide a simple and economical solution to validation steps that can be cumbersome with large homologous sequences, facilitating access to the production of therapeutic resources or disease models based on BAC-mediated homologous recombination.

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TP53 Gene 72 Arg/Pro (rs1042522) single nucleotide polymorphism increases the risk and the severity of chronic lymphocytic leukemia

Cited by 5 publications

References 51 publications

Morphological, clinical, and molecular profiling of post-polycythemia vera accelerated/blast phase occurring with and without antecedent secondary myelofibrosis

Morphological, clinical, and molecular profiling of post-polycythemia vera accelerated/blast phase occurring with and without antecedent secondary myelofibrosis

Genetic variability profiling of the p53 signaling pathway in chronic lymphocytic leukemia. Individual and combined analysis of TP53, MDM2 and NQO1 gene variants

Single Nucleotide Polymorphism-based Identification of Bacterial Artificial Chromosome-mediated Homologous Recombination

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