Dr. Mullighan on Germline Predisposition to ALL

Charles G. Mullighan, MBBS, MSc, MD, member, St. Jude Faculty, deputy director, Comprehensive Cancer Center, co-leader, Hematological Malignancies Program, medical director, St. Jude Biorepository, William E. Evans Endowed Chair, St. Jude Children’s Research Hospital, discusses germline predisposition to acute lymphoblastic leukemia (ALL).

In understanding germline predisposition to ALL, it is important to comprehend the genetic variants of the disease, says Mullighan—specifically, whether they’re silenced and noncoding or whether they’re non-silenced and have a direct effect on genes. Another question to address is whether these variants are present in families with a history of cancer. However, Mullighan notes that similar germline mutations can be found in the absence of a family history.

It is now known that there can be a strong relationship between an individual gene or mutations within that gene and features of the leukemia, says Mullighan. These can be found in specific cases of tumor-acquired or somatic events. Recent data suggest that specific genes, in the presence of specific germline mutations, are more amenable to certain therapies, he adds. These findings have led to a new paradigm in which determining genetic variants is of the utmost importance.