A combination of genetic mutations may explain the higher incidence of and poorer outcomes from pediatric leukemia in Hispanic and Latino children, according to Penn State College of Medicine researchers as reported in a news release. They said a novel therapeutic drug combination — as well as testing for these mutations — may help address the disparity.
Hispanic and Latino children are between 1.2 and 1.75 times more likely to develop B-cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer than non-Hispanic and Latino children. They also have a 40 percent higher death rate than their counterparts after correcting for socioeconomic factors.
The researchers studied 239 pediatric patients with B-ALL at Children’s Hospital Los Angeles and found two types of genetic mutations occurred more frequently in Hispanic and Latino children. Those mutations were a deletion of the IKZF1 gene (IKZF1), which holds instructions for cells to make the IKAROS protein and a rearrangement, or translocation, of the gene with instructions for producing the CRLF2 protein. The IKZF1 deletion occurred two times more frequently in those children, making it the most frequent genetic alteration that signals poor prognosis of B-ALL. There was a four-fold increased incidence of CRLF2 translocations in Hispanic and Latino children, as compared to non-Hispanic children.
The researchers also found that 11 percent of Hispanic and Latino children had both mutations compared to 0 percent of their counterparts. Almost all of the Hispanic and Latino children with B-ALL who had a specific type of CRLF2 translocation also had an IKZF1 deletion, while a large number of them had an IKZF1 deletion without that specific type of CRLF2 translocation.
According to the researchers, these results suggest that IKZF1 deletion precedes or predisposes the CRLF2 gene to mutation. The findings were published in the journal Leukemia.
In a companion study, also published in Leukemia, the researchers outlined a treatment strategy that may be beneficial to patients suffering from this health disparity. It involves targeting a protein, mTOR, that when over produced, can lead to resistance to chemotherapy and poor prognosis.
The researchers developed a combination therapy, starting with a drug that restores the function of IKAROS by inhibiting another protein called casein kinase 2 (CK2). When CK2 is prevented from carrying out its function, the IKAROS protein can keep mTOR from being produced. The team also used a second drug called rapamycin to inactivate mTOR proteins already present in cancer cells.
