6 research outputs found
Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL
The (12;21) translocation resulting in TEL/AML1 gene fusion is present in
about 25% of childhood precursor B-lineage acute lymphoblastic leukemia
(ALL) and is associated with a good prognosis and a high cellular
sensitivity to L-asparaginase (L-Asp). ALL cells are thought to be
sensitive to L-Asp due to lower asparagine synthetase (AS) levels.
Resistance to L-Asp may be caused by an elevated cellular level of AS or
by the ability of resistant cells to rapidly induce the expression of the
AS gene on L-Asp exposure. AS may be a target regulated by t(12;21). We
studied the relationship between t(12;21) and the mRNA level of AS to
investigate a possible mechanism underlying L-Asp sensitivity. Real-time
quantitative reverse transcription-polymerase chain reaction (RT-PCR)
analysis surprisingly revealed that 30 patients positive for t(12;21)
expressed 5-fold more AS mRNA compared with 17 patients negative for
t(12;21) (P =.008) and 11 samples from healthy controls (P =.016). The
mRNA levels of AS between t(12;21)(-) ALL and healthy controls did not
differ. No difference was found between ALL patients positive or negative
for t(12;21) in the capacity to up-regulate AS after in vitro L-Asp
exposure, excluding a defective capacity for t(12;21) cells in
up-regulating AS on L-Asp exposure. Moreover, no correlation was observed
between AS mRNA expression and sensitivity to L-Asp. We conclude that the
sensitivity of t(12;21)(+) childhood ALL to L-Asp is not associated with
the expression level of the AS gene. Furthermore, we contradict the
general thought that leukemic cells specifically lack AS compared with
normal bone marrow and blood cells
Hydrodynamics of DNA confined in nanoslits and nanochannels
Modeling the dynamics of a confined, semi exible polymer is a challenging problem, owing to the complicated interplay between the configurations of the chain, which are strongly affected by the length scale for the confinement relative to the persistence length of the chain, and the polymer-wall hydrodynamic interactions. At the same time, understanding these dynamics are crucial to the advancement of emerging genomic technologies that use confinement to stretch out DNA and “read” a genomic signature. In this mini-review, we begin by considering what is known experimentally and theoretically about the friction of a wormlike chain such as DNA confined in a slit or a channel. We then discuss how to estimate the friction coefficient of such a chain, either with dynamic simulations or via Monte Carlo sampling and the Kirk-wood pre-averaging approximation. We then review our recent work on computing the diffusivity of DNA in nanoslits and nanochannels, and conclude with some promising avenues for future work and caveats about our approach