16 research outputs found
The frequency of NPM1 mutations in childhood acute myeloid leukemia
<p>Abstract</p> <p>Background</p> <p>Mutations in the nucleophosmin <it>(NPM1) </it>gene have been solely associated with childhood acute myeloid leukemia (AML). We evaluated the frequency of <it>NPM1 </it>mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common <it>FLT3 </it>and <it>RAS </it>mutations.</p> <p>Results</p> <p><it>NPM1 </it>mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290) and (S293) in the NPM protein. <it>FLT3</it>/ITD mutations were observed in 12% of the cases and in one <it>NPM1-</it>mutated case bearing also t(8;21) (q22;q22). No common <it>RAS </it>mutations were identified.</p> <p>Conclusions</p> <p>A relatively consistent <it>NPM1 </it>mutation rate was observed, but with variations in types of mutations. The role of different types of <it>NPM1 </it>mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.</p
Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression
Resistance or sensitivity to glucocorticoids is considered to be of
crucial importance for disease prognosis in childhood acute
lymphoblastic leukemia. Prednisolone exerted a delayed biphasic effect
on the resistant CCRF-CEM leukemic cell line, necrotic at low doses and
apoptotic at higher doses. At low doses, prednisolone exerted a
pre-dominant mitogenic effect despite its induction on total cell death,
while at higher doses, prednisolone’s mitogenic and cell death effects
were counterbalanced. Early gene microarray analysis revealed notable
differences in 40 genes. The mitogenic/biphasic effects of prednisolone
are of clinical importance in the case of resistant leukemic cells. This
approach might lead to the identification of gene candidates for future
molecular drug targets in combination therapy with glucocorticoids,
along with early markers for glucocorticoid resistance. (C) 2009
Elsevier Ltd. All rights reserved
Computational Analysis of BRCA1 Mutations in Pediatric Patients with Malignancies and Their Mothers BRCA1 and BRCA2 Mutations in Childhood ALL
Breast and ovarian cancers are the most prevalent type of malignancies
amongst women. Similar incidence appear in childhood malignancies, where
the basic ontogenetic mechanisms still remain to be elucidated. Such
approaches, of relating mother's cancer mutations with the prevalence of
childhood cancer in their offspring could prove useful in the prognosis,
early detection and therapy of childhood malignancies. The aim of the
present study was to use computational and bioinformatics tools to
investigate the incidence of mutations in mothers with children
suffering from neoplasms. Genes were examined for mutations and in
particular, those were BRCA1, RAS family genes, TP53 and FLT3. Mutations
were initially detected using PCR and multiplex Polymerase Chain
Reaction (PCR) methodologies. Gene expression was detected using
quantitative Reverse Transcription PCR (qRT-PCR) methodologies and
results have been confirmed with the sequencing method. Following
experimental analysis, bioinformatics analyses have been performed. In
the case of positive identification of mutations, molecular modelling
was used in order to study the effects of the mutations on the BRCA
protein and subsequent effects on binding to BARD1, a signaling molecule
down-stream of BRCA1, which participates in DNA repair pathways.
Concluding, it appeared that the presence of a mutation in the
aforementioned genes is not adequate for the disease to progress, yet it
can be considered as a serious factor for disease progression. Thus, it
appears that this phenomenon is of extreme interest and it should be
further investigated in a larger patient cohort