Biomedical Engineering Reference
In-Depth Information
10.1.3
Treatment Complications and Prognosis
The differentiation syndrome (previously called “ATRA syndrome”)
is a potentially deadly complication of the induction therapy in
cases with APL. It occurs in approximately 25% of patients treated
with ATRA or arsenic trioxide. Early recognition and aggressive
management are fundamental [51].
The prognosis for APL depends on a number of factors including
the WBC count at diagnosis, elderly age, expression of CD56 surface
marker and severity of bleeding complications [37]. Overall, at
present more than 90% of patients with newly diagnosed APL can
achieve complete remission, and nearly 80% can be cured by the
combination of ATRA and chemotherapy [54].
10.2 Molecular Pathogenesis
10.2.1
Translocation (15;17) and Cloning of the Fusion
Gene
In over 95% of cases, APL occurs due to the t(15;17)(q22;q11-q12)
translocation, reported by Rowley
as a consistent feature of
this leukaemia subtype in 1977 [52]. This translocation is not a
mere marker of APL, but a causative event in the development of the
disease.
At a molecular level, as determined by Borrow
et al.
et al.
[7], Alcalay
et
al.
[16] in 1991, t(15;17) disrupts and fuses the
promyelocytic leukaemia (PML) gene located on chromosome 15 to
the retinoic acid receptor α (RARα) gene on chromosome 17, leading
to the formation of the PML/RARα fusion gene, and consequently,
of a chimeric protein. In view of the reciprocity of the translocation
also a RARα/PML fusion forms; however, its presence is not reliably
detected in all of the patients suggesting that PML/RARα, and not its
reciprocal translocation product, plays a more important role in the
leukaemogenesis [2].
Importantly, all diagnostic tests take advantage of the presence
of this unique chromosomal translocation in APL and its product -
PML/RARα fusion gene. The methods include cytogenetic analysis,
fluorescence
[3] and de The
et al.
hybridisation (FISH), PML immunofluorescence
(IF) staining and reverse-transcriptase polymerase chain reaction
in situ
