Biomedical Engineering Reference
In-Depth Information
the homodimer, facilitating further oligomerisation of PML and
PML/RARα. The resultant multimers form matrix-associated NBs
that are subsequently SUMOylated by UBC9 enzyme followed by
RNF4 ubiquitin E3 ligase-mediated ubiquitination and proteasomal
degradation [29, 63] (Fig. 10.1).
Table 10.1
The comparison of effects of treatment with ATRA and arsenic
trioxide
ATRA
Arsenic trioxide
Effect on blast cells Differentiation
Partial differentiation and
apoptosis
Effect on the PML/
RARα protein
Degradation of PML/
RARα by caspase-
driven cleavage and
ubiquitin/proteasome
system
Autophagy
SUMOylation of PML/
RARα that targets it
for ubiquitin-mediated
degradation
Autophagy
Target moiety
Acts on the RARα
moiety
Acts on the PML moiety
Effect on LICs
Decreases the number
of LICs, but rarely
eradicates them
Eradicates LICs,
especially when used in
combination with ATRA
Effect on NBs
Reformation of NBs Reformation of NBs
Overall outcome of
therapy
Frequent relapses and
rarely curative when
used on its own
Cases of cure described in
literature
Effect on
transcriptome
Release of the
transcriptional block-
potent transcriptional
regulation
Less genes regulated,
many of the genes
regulated by arsenic are
also regulated by ATRA
and to a greater extend
Effect on proteome Little effect
Profound change in
proteome pattern
-6
Low doses of arsenic (<0.5 × 10
M) tend to promote
differentiation of APL blasts, whereas high doses (0.5 × 10
-6
to 2
× 10
-6
M) induce apoptosis. The duration of exposure also plays a
