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Chapter 11 Haematological malignancy: aetiology and genetics / 165

5 4 10 –1

Intensity of fluorescence 3 2 10 –3 FU1
–2
10
–4
10

FU2

0 1

0 4 8 12 16 20 24 28 32 36 40 44
Cycle number

Figure 11.17 Real - time quantitative polymerase chain reaction (PCR) in acute B - lineage lymphoblastic leukae-
mia for minimal residual disease using the immunoglobulin heavy chain as target. Primers are designed based
on DNA from sequence analysis of the presenting leukaemic clone. Bone marrow samples taken in clinical
remission are amplifi ed by PCR using these primers and fl uorescent labelled using Sybergreen. The intensity of
the signal measures the total DNA molecules amplifi ed in successive cycles. In this example, the intensities of
amplifi cation of DNA from two follow - up bone marrow samples (FU1 and FU2) are compared with serial
− 1
− 4
deletions of (10 to 10 ) of the DNA from the presentation bone marrow. FU1 shows a level of residual disease
of approximately 1 in 5000 (0.02%) and FU2 of 1 in 12 000 (0.008%). (Courtesy of Dr L. Foroni.)

■ The haemopoietic malignancies are to increased activation of oncogenes or

clonal diseases that derive from a single decreased activity of tumour suppressor
cell in the marrow or peripheral lymphoid genes.

tissue which has undergone genetic ■ These genetic alterations may occur SUMMARY

alteration. through a variety of mechanisms such as

■ They represent approximately 7% of all point mutation, chromosomal
malignant disease. translocation or gene deletion.

■ Inherited and environmental factors both ■ Important investigations include study of

predispose to tumour development but the chromosomes (karyotype analysis),
the relative contribution of these is FISH, PCR, microarray analysis, fl ow
usually unclear. cytometry and immunohistochemistry.
■ Infections (viral and bacterial), drugs, ■ These investigations guide the diagnosis,

radiation and chemicals can all increase treatment and monitoring for residual
the risk of developing a haemopoietic disease of individual cases.
malignancy.
■ Haematological malignancies occur

because of genetic alterations that lead
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