Acute myelogenous leukemia in a patient with Li–Fraumeni syndrome treated with valproic acid, theophyllamine and all-trans retinoic acid: a case report

Ånensen, Nina; Skavland, Jørn; Stapnes, Camilla; Ryningen, Anita; Børresen‐Dale, Anne‐Lise; Gjertsen, Bjørn Tore; Bruserud, Øystein

doi:10.1038/sj.leu.2404117

Cited by 11 publications

(12 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This can provide a probable justification for the multiple functions played by p53 protein within the cell. The experimental data also suggests an abnormal expression of p53 isoforms in head and neck cancers (Boldrup et al, 2007), acute myeloid leukemia (Anensen et al, 2006) and cell lines (Goldschneider et al, 2006). Thus, suggesting altered p53 isoforms expression pattern could disrupt p53 function and also be fundamental to tumor formation.…”

Section: Discussionmentioning

confidence: 76%

p53 and little brother p53/47: linking IRES activities with protein functions

et al. 2009

View full text Add to dashboard Cite

The tumor suppressor p53 represents a paradigm for gene regulation. Its rapid induction in response to DNA damage conditions has been attributed to both increased half-life of p53 protein and also increased translation of p53 mRNA. Recent advances in our understanding of the post-transcriptional regulation of p53 include the discovery of internal ribosome entry sites (IRESs) within the p53 mRNA. These IRES elements regulate the translation of the full length as well as the N-terminally truncated isoform, p53/47. The p53/47 isoform is generated by alternative initiation at an internal AUG codon present within the p53 ORF. The aim of this review is to summarize the role of translational control mechanisms in regulating p53 functions. We discuss here in detail how diverse cellular stress pathways trigger alterations in the cap-dependent and cap-independent translation of p53 mRNA and how changes in the relative expression levels of p53 isoforms result in more differentiated p53 activity.

show abstract

Section: Discussionmentioning

confidence: 76%

p53 and little brother p53/47: linking IRES activities with protein functions

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Decitabine and 5-azacytidine both inhibit methylation and seem to have antileukemic effects, but they also have toxic effects on normal bone marrow and are associated with a risk of peripheral blood cytopenia [103,104]. Several HDAC inhibitors have also been investigated in clinical trials, and peripheral blood cytopenia is a common side effect for most of these mediators [105,106]. However, the use of valproic acid in the treatment of AML may represent an exception because the initial platelet decrease may then be followed by increased platelet counts at least for a subset of patients [105,106].…”

Section: Epigenetic Therapymentioning

confidence: 98%

The Combination of Conventional Chemotherapy with New Targeted Therapy in Hematologic Malignancies: The Safety and Efficiency of Low- Dose Cytarabine Supports its Combination with New Therapeutic Agents in Early Clinical Trials

Fredly¹,

Ersvær²,

Stapnes³

et al. 2009

CCTR

View full text Add to dashboard Cite

Cytarabine (cytosine arabinoside) is commonly used in the treatment of hematologic malignancies, including both myeloid and lymphoid disorders. The cytotoxic effect of the drug depends on conversion to its triphosphate form in the targeted cells, and the intracellular levels of this active form depend on the balance between phosphorylating and dephosphorylating enzymes. The sensitivity to cytarabine-triphosphate induced cytotoxicity is in addition dependent on the balance between pro-and antiapoptotic signalling in the malignant cells, especially the balance between various members of the bcl-2 family. Even though differentiation induction has been claimed to be important in low-dose cytarabine, most clinical studies suggest that the cytotoxic affect is most important even in this therapeutic strategy. The clinical experience with the low-dose therapy is based on studies in hematological malignancies, mainly acute myeloid leukemia and myelodysplastic syndromes. These studies clearly document the clinical efficiency of low-dose therapy. However, even this low-dose strategy has a risk of severe hematological toxicity and eventually serious or fatal infections especially in elderly patients. Our understanding of the molecular mechanisms behind chemoresistance and chemosensitivity to cytarabine thereby forms the scientific basis for the design of future clinical studies where cytarabine can be combined with new targeted therapy. Low-dose cytarabine may then represent an efficient alternative with an acceptable toxicity even when combined with new anticancer agents in early clinical studies. However, the possibility of pharmacological interactions with the intracellular metabolism of cytarabine by these new agents has to be considered when combination regimens are designed.

show abstract

“…7 Patients with germline TP53 mutations have an increased risk of developing acute myeloid leukemia and MDS. [18][19][20] The genetics are described in more detail in the Online Supplementary Results.…”

Section: Aplastic Anemia Geneticsmentioning

confidence: 99%