Page 251 - Essential Haematology

Chapter 18 Chronic lymphoid leukaemias / 237

IgD). This is shown to be monoclonal because of 11q23 (aff ecting the ATM gene), structural

expression of only one form of light chain ( κ or abnormalities of 17p involving the p53 gene and
λ ; Table 18.2 ). Characteristically, the cells are 6q21 deletion. Th ese abnormalities carry prognostic
+
−
+
also surface CD5 and CD23 but are CD79b signifi cance (Table 18.3 ). Th e 13q14 deletion leads
−
and FMC7 (Fig. 18.4 ). to loss of microRNAs which normally control
3 Normochromic normocytic anaemia is present in expression of proteins that regulate B - cell survival
later stages as a result of marrow infi ltration or (see p. 160 ).
hypersplenism. Autoimmune haemolysis may
also occur (see below). Th rombocytopenia occurs Somatic h ypermutation of the

in many patients. i mmunoglobulin g enes
4 Bone marrow aspiration shows lymphocytic When B cells recognize antigen in the germinal
replacement of normal marrow elements. centre of secondary lymphoid tissues they undergo
Lymphocytes comprise 25 – 95% of all the cells. a process called somatic hypermutation in which

Trephine biopsy reveals nodular, diffuse or inter- random mutations occur in the immunoglobulin
stitial involvement by lymphocytes (Fig. 18.5 ). heavy - chain gene. In CLL, the IGVH gene shows
5 Reduced concentrations of serum immunoglob- evidence of this hypermutation in approximately
ulins are found and this becomes more marked 50% of cases whereas in the other cases the VH
with advanced disease. Rarely, a paraprotein is genes are unmutated. CLL with unmutated immu-
present. noglobulin genes has an unfavourable prognosis
6 Autoimmunity directed against cells of the hae- (Table 18.3 ).
mopoietic system is common. Autoimmune
haemolytic anaemia is most frequent but immune Tumour c ell p henotype

thrombocytopenia (see p. 334 ) , neutropenia and ZAP - 70 is a protein tyrosine kinase that is

red cell aplasia are also seen. involved in cell signalling following recognition
of antigen by antigen receptors on lymphocytes.
Its expression is normally restricted to T cells but
Prognostic m arkers
it is also aberrantly expressed in cases of CLL where
Cytogenetics it is associated with an unfavourable clinical
The most common chromosome abnormalities outcome. Strong expression of CD38 also is an

are deletion of 13q14, trisomy 12, deletions at unfavourable prognostic feature.

+

Table 18.2 Immunophenotype of the chronic B - cell leukaemias/lymphomas (all cases CD 19 ).
CLL PLL HCL FL MCL

SIg Weak + + + + + + +

CD5 + − − − +
CD22/FMC7 − + + + + +

CD23 + − − − −

CD79b − + + − / + + + + +

CD103 * − / + − + − −
CLL, chronic lymphocytic leukaemia; FL, follicular lymphoma; HCL, hairy cell leukaemia; MCL, mantle cell lymphoma; PLL,
prolymphocytic leukaemia.

* CD103 is positive only in HCL.