Abstract:
Chronic myelogenous leukaemia (CML) is a myeloproliferative disorder that
results from the neoplastic transformation of haematopoietic progenitor cells. It
accounts for 15-20% of leukaemias in adults and occurs with an incidence of 1-2
cases per 100 000 population, and the patients have a median survival period of
3-4 years from diagnosis.
Knowledge of normal haematopoiesis has increased the understanding of how
specific perturbations may lead to the development of a transformed or malignant
phenotype that is now clinically recognized as leukaemia. The discovery of
oncogenes initiated a laboratory effort where the focus was to elucidate as yet
undescribed oncogenes and to understand how single allele mutations could act
dominantly in the "gain of function" ability to transform cells and cause tumours.
These investigations obscured the existence of another set of genes which also
appeared to be permissive of tumour formation. In contrast to the oncogenes,
these genes behaved in a recessive manner so that "loss of function" as opposed
to "gain of function", resulted in tumour formation. These genes therefore
appeared to behave as tumour suppressor genes.
The role of tumour suppressor genes is to prevent tissue overgrowth, nullify cells
with damaged genomes, and metastasis. The structure and expression of the
p53 gene is altered in about 25% of myeloid blast crisis of CML, whereas chronic phase CML rarely has detectable p53 alterations, suggesting that mutations in
the p53 gene might be involved in the evolution of some cases of blast crisis.
Oncogenes are genes that have the ability to transform normal cells into cancer
cells. Not all O-type cyclins are expressed in each tissue, suggesting that their
function may be linked to the specific tissues in which they are expressed.
Increased expression of cyclin 01 can playa critical role in tumour development
and in maintenance of the malignant phenotype, thus over-expression of cyclin
01 can produce complex effects on various cellular functions involved in growth
control and cell cycle progression.
Fluorescence in situ hybridization (FISH) allows the detection of numerical
aberrations in interphase cell nuclei and provides a simple, fast and reliable
means to assess genetic instability in cancer ce lls.
Significant p53 loss of allele was detected in 6 out of 25 samples, indicating that
the p53 tumour suppressor gene can be involved in the progression of CML from
chronic phase to blastic phase. Cyclin 01 amplification was not detected in any
of the samples investigated by FISH, indicating that cyclin 01 is not expressed in
cells of the lymphoid and myeloid lineages.
Keywords: chronic myelogenous leukaemia, p53, cyclin 01, fluorescence in
situ hybridization
