Biomedical Engineering Reference
In-Depth Information
the formation of reactive oxygen species, consequently affecting
numerous signalling pathways. Both agents target the fusion protein
for degradation, albeit via diverse mechanisms. Moreover, ATRA
synergises with arsenic in eliminating leukaemia-initiating cells
(LICs) also referred to as leukaemic stem cells (LSC). The progress
made in the treatment of patients with APL constitutes an example
of a success story of translational haematology towards which both
basic scientists and clinicians have contributed over the years.
10.1 Introduction
Acute promyelocytic leukaemia, commonly called APL, is a malignan-
cy of the bone marrow in which there is a deficiency of mature blood
cells of the myeloid lineage and an excess of immature cells blocked
at the promyelocyte stage of the differentiation. APL accounts for
5-10% of cases of acute myeloid leukaemia. The peak incidence of
APL is ~40 years of age. It was classified as the M3 variant of AML of
the French-American-British (FAB) Classification [5].
APL was first recognised as a distinct disease entity in 1957
[27]. The original description underlined a very rapid downhill
course, with survival rates of only few weeks from diagnosis, mainly
due to the severe bleeding tendency caused by fibrinolysis and
thrombocytopaenia. Indeed, from 1950s until the introduction of
anthracyclins into the chemotherapeutic regimens in the 1970s [6],
APL had a 100% mortality rate, as there was no effective treatment.
10.1.1
Description of Acute Promyelocytic Leukaemia
The signs and symptoms of APL are non-specific and include fatigue,
minor infections and a haemorrhagic diathesis manifesting itself as
petechiae, small ecchymosis, epistaxis, or in more extreme cases,
bleeding from the mouth or venipunctures and haematuria. The
haemorrhagic diathesis may precede the diagnosis of leukaemia by
2-8 weeks [17].
Microscopically, typical promyelocytic malignant cells are found
in bone marrow aspirates, and less frequently, in the peripheral
blood while the white blood cell count (WBC) remains low. The
predominant malignant cells are abnormal promyelocytes, with an
