Re: Prognostic Significance of a Short Sequence Insertion in the MCL-1 Promoter in Chronic Lymphocytic Leukemia

Extract

We read with great interest the recent article by Moshynska et al. ( 1 ) in the Journal, which reported short sequence insertions in the MCL-1 promoter of B-cell chronic lymphocytic leukemia (B-CLL) samples. The authors analyzed genomic DNA from B-CLL cells of 58 B-CLL patients and from lymphocytes of 18 healthy control donors. The sequence of the promoter region of the MCL-1 gene revealed the presence of a 6- or 18-base pair insertion in approximately 30% of the B-CLL samples. In contrast, and very interestingly, these insertions were completely absent in all healthy control subjects and in the normal soft tissues from two B-CLL patients whose lymphocytes harbored these insertions. These alterations would appear to represent one of the most frequent somatic genomic alterations described so far in B-CLL patients, and these results deserved an editorial in the same issue of the journal ( 2 ) .

To confirm the presence of these insertions in the B-CLL samples from patients at our hospital, Hospital Universitari de Bellvitge, we obtained the corresponding MCL-1 gene promoter region from the genomic DNA of lymphocytes from 26 B-CLL patients. From each genomic DNA sample, the putative presence of the insertions was analyzed in both alleles by polymerase chain reaction amplification and electrophoresis analysis. Each amplified band was eluted from the gel, purified, and sequenced. The nucleotide sequences obtained for this region corroborated the three variants observed in the electrophoresis, corresponding to the absence of insertion, the 6-nucleotide insertion, and the 18-nucleotide insertion ( Table 1 ).