Genetics and Childhood Leukemia

According to the Leukemia and Lymphoma Society and the National Cancer Institute (both U.S.), leukemia is a disorder in which the body's bone marrow releases an abnormal number of immature white blood cells (the cells that fight infection) into the bloodstream. Acute lymphoblastic leukemia (ALL) is particularly notorious for its rapid progression if not diagnosed early in its course and treated aggressively in the 5,000 new cases of ALL that are reported each year in the United States

Among cancer treatment specialists (oncologists), it has been long noted that Native American and Hispanic children have a much poorer response, as well as a higher relapse rate, to treatment for certain forms of leukemia, particularly in acute lymphoblastic leukemia (ALL) than that seen in members of other ehtno-racial groups. Although this poorer response has been almost invariably ascribed to socio-economic factors, a recent study in Nature Genetics strongly suggests that a genetic factor is the more likely explanation.

In the published report, a team of investigators led by oncologists from St. Jude Children's Research Hospital analyzed the genomes of some 2,500 children with a confirmed diagnosis ALL. At the end of their study, the researchers found that two specific genetic markers "JAK" and "CLRF2" were found in close association with ALL. It was when ethnic / demographic data were considered that the "consensus opinion boat was rocked."

The study, which was based on response to the standard course of treatment received by all patients, found that both genetic markers were associated with either (1) a failure of ALL to respond to treatment or (2) with an earlier relapse of what had been an effective treatment regimen and that these markers were consistently present in children of self-identified Native Americans and in Hispanics that reported a first- or second-degree Native American ancestor. Furthermore, the overall incidence of these markers in the Native American / Hispanic populations closely follows the previously-observed treatment failure and / or relapse rates in those groups.

In a recent interview published in the Albuquerque Journal Dr. Cheryl Willman, the director of the University of New Mexico Cancer Center and a co-author of the St. Jude study as well, described the early controversy generated by the researchers.

After noting that many researchers have offered socio-economic explanations for the drastic differences reported between Native / Hispanic and other ethnic groups by speculating that Hispanic and Native American families fail to seek care or don't finish their therapy, she rebutted these explanations by noting that the children who were involved in the study were treated using identical protocols and that all had completed their therapies.

The study ""is one of the strongest proofs that your race and ethnicity, determined by genetic ancestry, really predicts your response to cancer therapy ... People will be shocked ..." by its results she said.

Commentary

With the exceptions of maternal prenatal exposure to ionizing radiation and its known association with some trisomy syndromes (e.g Down syndrome), the exact etiology ("cause") of childhood leukemia remains unclear. The above-mentioned report is interesting in that it has identified a specific genetic marker which can predict, with an acceptable degree of accuracy, the prospect of an early relapse during treatment for ALL. However, as with other early results defining the role of genetics in the later development of specific disease conditions, there are ethical issues that will certainly arise and such issues must be addressed.

See Also

Jun J Yang, Cheng Cheng, Meenakshi Devidas, and Xueyuan Cao et al. "Ancestry and Pharmacogenomics of Relapse in Acute Lymphoblastic Leukemia." Nature Genetics (2011) 43: 237-241. doi:10.1038/ng.763 (Abstract).

The potential implications of the JAK and CLRF2 genetic markers are discussed here and here, respectively.

National Cancer Institute Fact Sheet. "A Snapshot of Pediatric Cancer."

American Association of Cancer Researchers. "Putting Knowledge To Work: The Genetics of Cancer."