Page 171 - Essential Haematology

Chapter 11 Haematological malignancy: aetiology and genetics / 157

Figure 11.6 A colour - banded karyotype from a normal male. Each chromosome pair shows an individual
colour - banding pattern. This involves a cross - species multiple colour chromosome banding technique. Probe
sets developed from the chromosomes of gibbons are combinatorially labelled and hybridized to human
chromosomes. The success of cross - species colour banding depends on a close homology between host and
human conserved DNA, divergence of repetitive DNA and a high degree of chromosomal rearrangement in the
host relative to the human karyotype. (Courtesy of Dr C.J. Harrison.)

classified according to genetic change rather than
Telomere

3 morphology. The types of gene abnormality include
2 2 the following (Fig. 11.8 ).
1
p
2
1 Point m utation
1
Centromere

1 This is best illustrated by the Val617Phe mutation
in the JAK2 gene which leads to constitutive activa-
1 2
tion of the JAK2 protein in most cases of myelo-
3

q proliferative disease (see Chapter 15 ). Mutations of
1 TET - 2, a probable tumour - suppressor gene, occur
2 in up to 20% of myeloid neoplasms except chronic
2
3
myeloid leukaemia (CML ) and may be an earlier
4
Telomere event than the JAK2 mutation. Mutations within
the RAS oncogenes or p53 tumour - suppressor gene
Bands are common in many haemopoietic malignancies.
Regions

The point mutation may involve several base pairs.
In 35% of cases of AML the nucleophosmin gene

Figure 11.7 A schematic representation of a chromo-

shows an insertion of four base pairs resulting in a
some. The bands may be divided into subbands
frameshift change. Internal tandem duplication or
according to staining pattern.
point mutations occur in the FLT - 3 gene in 30% of
Genetic a bnormalities a ssociated cases of AML.
with h aematological m alignancies
Translocations

The genetic abnormalities underlying the diff erent
types of leukaemia and lymphoma are described Th ese are a characteristic feature of haematological
with the diseases which are themselves increasingly malignancies and there are two main mechanisms