ETIOLOGY OF LEUKEMIA
The causes of leukemia are still unknown, however a virus called
Feline leukemia virus has been shown to cause leukemia in cats. There is no
evidence for viral etiology in man except for a specific subtype found predominantly
in the southern islands of japan and the Caribbean with retrovirus HTLV-1. It
is surprising that despite most people in the endemic areas having antibodies
to this virus (signaling past infection by it), most of them will never develop
leukemia. A combination of genetic and environmental factors are the greatest
suspects on how leukemia comes about.
Genetic factors
Leukemias result from the transformation and clonal expansion of
progenitor cells in the bone marrow. There exists a difference in expression of
the disease between younger and older patients in that in older patients, its
most likely to arise from pluripotent stem cell than from progenitor cells in
children. This makes it harder to treat in older patients since the cells have
a high capacity for self-renewal and possess an active drug-efflux pump
mechanism, together with a high content of antiapoptotic proteins, making them
more chemo-resistant.
Leukemias arise from cytogenetic abnormality in which a portion of
chromosome that joins two chromosomes; chromosomes 22 and 9 is reciprocally translocated
leading to an abnormal chromosome called Philadelphia chromosome. This chromosome
leads to the coding (production) for a hybrid protein: a tyrosine kinase signaling protein.
Tyrosine
kinase is a protein responsible for signaling of the cells to initiate production
of cells in normal growth, repair and development processes in the body. It works
as an on and off switch. It goes on when there’s need and off when the need is met.
However, in the presence of Philadelphia chromosome, a hybrid of it, (the tyrosine kinase signaling protein) that
is produced is "always on",
causing the cell to divide uncontrollably by interrupting the stability of the
genome and impairing various signaling pathways governing the cell cycles.
Environmental Factors
Genetic factors can either be spontaneous or spurred by the
environment. Chemicals and their
activity in the environment in which an individual stays may have a direct
contribution to the mutations seen in most cancers.
The environmental factors can be classified into chemicals (benzene
compounds), drugs (alkylating agents), radiation. Historical incidences
illustrate how radiation has effect on those that are exposed to it.
- Atomic explosions at Hiroshima and Nagasaki resulted in increased incidences of both AML and CML in people living in the surrounding areas.
- Patients with ankylosing spondylitis in the past were treated with radiotherapy leading to increased incidence of secondary AML
- A proportion of patients with Hodgkin’s disease treated with both chemotherapy and radiotherapy develop secondary AML
Unlike the
primary spontaneous/genetic type of leukemias that are easily treatable, secondary
leukemias developing as a result of previous chemotherapy or radiation treatment
are hard to treat and are nearly always resistant.
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