Page 178 - Essential Haematology

164 / Chapter 11 Haematological malignancy: aetiology and genetics

Figure 11.15 Immunohistologic
detection of BCL - 2 protein in
reactive and neoplastic lymphoid
cells. (a) A follicular lymphoma is
positive, refl ecting activation of
the BCL - 2 gene by the (14;18)
translocation. (b) In reactive
lymphoid tissue unstained
germinal centres are surrounded
by numerous positive mantle
(a) (b) zone B and T cells.

For e stablishing a t reatment p rotocol
Each major type of haematological malignancy 10 0
can be further subdivided on the basis of detailed
genetic information. For instance, AML is a 10 1
diverse group of disorders with characteristic gen- Morphology
otypes. Individual subtypes respond diff erently to 10 2
Cytogenetics

standard treatment. The t(8; 21) and inv(16) sub-
groups have a favourable prognosis, whereas 10 3
Immunological
monosomy 7 carries a poor prognosis. Treatment markers
strategies are now tailored for the individual and 10 4 PCR
in some instances knowledge of the underlying
genetic abnormality can lead to more rational 10 5

treatment, e.g. the use of all - trans retinoic acid
in acute promyelocytic leukaemia with t(15; 17) 10 6
(see p. 186 ). For BCR – ABL1 + CML and ALL,
drugs are now available that target the fusion

protein and improve overall survival. Figure 11.16 Sensitivity of detection of leukaemic
Genetic information is also valuable for giving cells in bone marrow using four different techniques.
6
1
6

10 to 10 = 1 cell in 10 to 1 cell in 10 detected.

a prognosis. For instance, hyperdiploidy in ALL is
a favourable fi nding.
1 Cytogenetic analysis.
2 Fluorescence - activated cell sorting to detect
Monitoring the r esponse to t herapy tumour cells using immunological markers that
detect ‘ leukaemia - specific ’ combinations of anti-

The detection of minimal residual disease (disease
gens (see Fig. 17.7 ).
that cannot be seen by conventional microscopy of
3 PCR to amplify tumour - specifi c translocations
the blood or bone marrow) in AML, ALL or CML
or immunoglobulin/TCR sequences specifi c to
or other haematological malignancies when the
the original clone (Fig. 11.17 ).
patient is in remission after chemotherapy or stem
cell transplantation is possible using the following These approaches have an important role in deter-

techniques (in increasing order of sensitivity; mining the treatment of many forms of haemopoie-
Fig. 11.16 ). tic malignancy.