BOF: Malignant (CLL)

Which of the following molecular markers conveys a relatively better prognosis subgroup in chronic lymphocytic leukaemia (CLL)?

a) CD38 surface marker positive by flow cytometry and immunophenotyping

b) Immunoglobulin heavy chain gene somatic hypermutation

c) Deletion of chromosome 11q detected by fluorescent in-situ hybridisation

d) Serum beta-2 microglobulin raised above 3.0mg/dl.

e) ZAP-70 positive by flow cytometery and immunophenotyping

Answer:

b) Immunoglobulin heavy chain gene somatic hypermutation

Explanation:

Positivity for CD38 and ZAP-70 as detected by flow cytometry are well-recognised poor prognostic markers in CLL. Deletions of 11q or 17p are also poor prognostic markers when detected by conventional metaphase spread karyotype or fluorescent in situ hybridisation (FISH). High beta-2 microglobulin is also associated with poor prognosis. One of the most powerful predictors of prognosis is the presence or absence of somatic hypermutation in the immunoglobulin heavy chain (IGHV) genes, with less than 2% difference from germline genes (unmutated status) being associated with a more aggressive disease. However, since this is a relatively expensive test which does not influence management, it is rarely performed outside the research context. P53 or 17p deletion is currently the only molecular risk stratifier used to modify treatment in widespread clinical use.

Reference:

Gribben J. How I treat CLL up front. Blood 2010;115(2):187-197