Page 167 - Essential Haematology

Chapter 11 Haematological malignancy: aetiology and genetics / 153

Infection genetic hit ’ within the tumour cell is unclear but
an abnormal response of the immune system to
Children may have a predisposition to acute lym-
infection is suggested by epidemiological studies.
phoblastic leukaemia (ALL) from their germline
Children with a high level of social activity, notably
constitution. A proportion of cases of childhood
those attending early nursery daycare, have a
ALL are then initiated by genetic mutations that
reduced incidence of ALL, whereas those living in
occur during development in utero (Fig. 11.3 ).
more isolated communities and who have a reduced
Studies in identical twins have shown that both may

exposure to common infections in the first years of
be born with the same chromosomal abnormality,
life have a higher risk.
e.g. t(12; 21). This has presumably arisen spontane-

ously in a progenitor cell that has passed from one
twin to the other as a result of the shared placental Viruses
circulation. Environmental exposure during preg-
nancy may be important for this first event. One Viral infection is associated with several types of

twin may develop ALL early (e.g. at age 4) because haemopoietic malignancy, especially diff erent sub-
of a second transforming event affecting the copy types of lymphoma (see Table 20.2 ). Th e retrovirus

numbers of several genes including those in B - cell human T - lymphotropic virus type 1 is the cause of
development and relevant to the leukaemogenesis. adult T - cell leukaemia/lymphoma (see p. 243 )
The other twin remains well or may develop although most people infected with this virus do

ALL later. Th e TEL - AML1 translocation is present not develop the tumour. Epstein – Barr virus (EBV)
in the blood of approximately 10% of newborn is associated with almost all cases of endemic
infants but only 1 in 100 of these go on to develop (African) Burkitt lymphoma, post - transplant lym-

‘
ALL at a later date. The mechanism of the second phoproliferative disease (which develops during
Primary event Secondary Secondary
t(12;21) event event
translocation

ALL
Twin 1

t(12;21)
ALL
Twin 2
In utero

–9 0 5 14
months Age (years)

Figure 11.3 Prenatal origin of acute lymphoblastic leukaemia (ALL) in a pair of identical twins. ALL was

diagnosed in the fi rst twin at age 5 years and in the second at age 14 years. Both tumours had an identical t(12;
21) translocation indicating probable origin of the leukaemic clone in utero and dissemination to both twins via a
shared placental blood supply. Because of the prolonged latency of the ALL it is presumed that a secondary
event is required to initiate the development of frank leukaemia. At the time of the diagnosis of ALL in twin 1 the
t(12; 21) translocation could be detected in the bone marrow of twin 2. It is likely that such a ‘ fetal origin ’ of
childhood ALL occurs in a signifi cant number of sporadic ALL cases. (After Wiemels J.L. et al. (1999) Blood
94 ,1057 – 62.)