Early Research Steps in Understanding APOBEC3B in Myeloma
Posted: Wednesday, August 28, 2019
If the DNA of myeloma cells can be envisioned as the “works,” then one “wrench” thrown into them that makes them especially difficult to conquer may be the overexpression of the molecule called endogenous APOBEC3B (A3B), research published in Science Reports revealed. 3B is a particular form of an APOBEC, short for apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like DNA cytosine deaminase. High A3B expression has been previously shown in breast cancer, and possibly in lung and ovarian cancers, to be related to treatment resistance, metastasis, and poor prognosis.
Akifumi Takaori-Kondo, MD, PhD, of Kyoto University in Japan, and colleagues attempted to understand A3B’s significance and clinical impact in multiple myeloma. Using quantitative polymerase chain reaction, they found that “among APOBECs, only highly expressed A3B was associated with poor prognosis in myeloma patients, independent of other known poor prognostic factors.”
Specifically, the investigators noted, “A3B knockdown…decreased the basal levels of γ-H2AX foci, suggesting that A3B promotes constitutive DNA double-strand breaks in myeloma cells.”
One part of their work involved examining cells from 414 patients with newly diagnosed multiple myeloma; notably, of the APOBECs studied, A3B alone was correlated with significantly worse overall survival. The 3-year overall survival for the A3B-high group was 66.2% versus 81.8% for the A3B-low group (P = .00133).
This was reportedly the first study to specifically investigate the workings of endogenous A3B and its ongoing mutagenic effects in myeloma cells, wrote Dr. Takaori-Kondo and his team. “Although the clinical impact of A3B-related oncogenesis in myeloma remains to be further evaluated, inhibiting A3B activity could protect against disease deterioration and could be a new therapeutic option,” they concluded.
Disclosure: The study authors reported no conflicts of interest.