Mcl-1 Promoter Insertions as an Independent Prognostic Factor for Treatment Free Survival in Chronic Lymphocytic Leukaemia.

Mcl-1 (Myeloid cell leukaemia 1) is an anti-apoptotic member of the Bcl-2 family of proteins and is known to be important in the biology of Chronic Lymphocytic Leukaemia (CLL). A study by Moshynska et al demonstrated that a 6 or 18 nucleotide promoter insertion within the Mcl-1 promoter region influenced clinical outcome in CLL. In this study the presence of the insertion was also associated with high Mcl-1 mRNA and Mcl-1 protein levels. Subsequently there have been a number of published reports showing that these insertions have no impact at all on survival or any role in the pathogenesis of CLL. Using PCR and WAVE analysis, we analysed both the 6–18bp Mcl-1 promoter insertions in a cohort of a 100 CLL patients and 100 normal controls. Mcl-1 promoter insertions occurred at a similar frequency in the control and CLL groups. Mcl-1 promoter insertions did not correlate with any of the established prognostic factors in CLL (CD38 expression, VH mutation status, LDT, Zap 70 and stage), did not correlate with Mcl-1 protein levels and did not influence overall survival (P values >0.05). However Mcl-1 promoter insertions significantly affected treatment free survival (P= 0.002). This result needs confirming in a larger number of patients as it suggests that promoter insertions identify patients that are more likely to require therapy and again raises the question of its role, if any, in CLL pathology.