Abstract:
Deletions and/or rearrangements on chromosome 13q14.3 are observed in more than half
of multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) cases and are also
frequently seen in other hematopoietic malignancies. The minimal common deleted
region (CDR) in MM cells contains candidate tumor suppressor gene KCNRG (potassium
channel regulating gene), the product of which suppresses assembly of the Kv channels
and Kv currents. KCNRG exerts growth suppressive and pro-apoptotic effects in HL-60,
LNCaP and RPMI-8226 cells. In this study, the KCNRG gene was sequenced in three
multiple myeloma cell lines, NCI-H929, RPMI-8226 and U266B2. The RPMI-8226 cell
line was found to contain a delT mutation in the core promoter initiator element. Deletion
of T decreases matrix similarity of this DNA element from 0.945 to 0.941, and, therefore,
might negatively influence expression of KCNRG in RPMI-8226 cells. The
haploinsufficiency of KCNRG might be relevant to the progression of CLL and MM at
least in a subset of patients.
