Page 168 - Essential Haematology

154 / Chapter 11 Haematological malignancy: aetiology and genetics

immunosuppressive therapy after solid organ trans- The g enetics of h aemopoietic

plantation (see p. 312 )) and a proportion of patients m alignancy
with Hodgkin lymphoma. Human herpes virus 8
(Kaposi ’ s sarcoma - associated virus) is associated Malignant transformation occurs as a result of the
’
with Kaposi s sarcoma and primary eff usion lym- accumulation of genetic mutations in cellular genes.

phoma (see Table 20.2 ). The genes that are involved in the development of
HIV infection is associated with an increased cancer can be divided broadly into two groups:
incidence of lymphomas at unusual sites such as the oncogenes and tumour - suppressor genes .
central nervous system. The HIV - associated lym-

phomas are usually of B - cell origin and of high -
Oncogenes
grade histology.
Oncogenes arise because of gain - of - function muta-
tions in normal cellular genes called proto - oncogenes
Bacteria
(Fig. 11.4 ). Proto - oncogenes are involved in a
Helicobacter pylori infection has been implicated in variety of important cellular processes, often in the
the pathogenesis of gastric mucosa B - cell (MALT) pathway by which external signals are transduced to
lymphoma (see p. 265 ). the cell nucleus to activate genes. Oncogenic ver-
sions are generated when the activity of proto -
oncogenes is increased or they acquire a novel
Protozoa
function. This can occur in a number of ways

Endemic Burkitt lymphoma occurs in the tropics, including translocation, mutation or duplication.
particularly in malarial areas. It is thought that One of the striking features of haematological
malaria may alter host immunity and predispose malignancies (in contrast to most solid tumours) is
to tumour formation as a result of EBV their high frequency of chromosomal transloca-
infection. tions. A subset of proto - oncogenes are involved in

NORMAL CELL
Proto-oncogene
Regulated
proliferation
and apoptosis
Tumour suppressor
gene

MALIGNANT CELL
Oncogene
Chemicals, Excess
radiation, proliferation
drugs, virus, and failure
translocation, of apoptosis
deletions Tumour suppressor
gene

Figure 11.4 Proliferation of normal cells depends on a balance between the action of proto - oncogenes and

tumour - suppressor genes. In a malignant cell this balance is disturbed leading to uncontrolled cell division.