Acute lymphoblastic leukemia (ALL), a cancer that starts from white blood cells in the bone marrow, is the most common form of leukemia in childhood and is a major cause of sickness and death in children. While the clinical and biological aspects of childhood leukemia are well documented, little is known about genetic factors that make an individual susceptible to develop leukemia. It is well known that there are differences in the incidence of childhood leukemia among the different ethnic groups with the highest rate in US Hispanics.
Our team found ethnic specific risk associations between ALL and variants in two genes, the mixed lineage leukemia gene (MLL) which was significantly associated with ALL in Hispanics (REF 1), and the LIM domain only 1 gene (LMO1) which was newly identified as a susceptibility locus in precursor B-cell ALL in Whites (REF 2).
The association of variants in MLL suggests that this gene may play a role in the increased risk of ALL and possibly treatment-related AML (t-AML) in Hispanics in Texas, a group that has been shown to have a unique sensitivity and increased incidence of secondary malignancies from exposure to topoisomerase II inhibitors. A more comprehensive evaluation of the genetic structure of the MLL gene will clarify its role in the unique sensitivity to topoisomerase II inhibitors in Hispanic children with leukemia (REF 1).
As LMO1 has not been previously identified as a susceptibility gene in pre-B cell leukemogenesis, we are currently exploring whether this gene has a role in children affected with this subtype (REF 2).
If a molecular basis for the predisposition to develop childhood ALL can be determined, it may be possible to predict which children are at risk of developing ALL or even t-AML.