According to a recent article published in the journal Blood, the expression of specific genes appear to be associated with resistance to certain treatment drugs, as well as overall outcomes, in pediatric patients with acute lymphoblastic leukemia. If confirmed, these results will help to individualize therapy for children diagnosed with this disease.

Acute lymphoblastic leukemia (ALL) is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells called stem cells. These grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to tissue; and platelets, which help blood to clot.

ALL is characterized by uncontrolled production of immature lymphocytes (white blood cells), which exist in two forms: B and T cells. These immature lymphocytes never develop enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells (such as red blood cells, platelets, and other white blood cells).

Pediatric ALL is not just one disease; there are many different subtypes of ALL, which are based on specific disease variables such as specific genetic abnormalities, levels of cancerous cells detected in the blood or bone marrow, and resistance to treatment. Patients who are resistant to treatment tend to have poorer outcomes than those who respond to treatment.

Researchers continue to evaluate different variables, such as mutations within specific genes, and their association with outcomes in pediatric ALL. Understanding possible associations prior to therapy can help guide individualized treatment for each patient.

Researchers from Germany, the Netherlands, and St. Jude’s Children Hospital in Tennessee recently conducted a clinical trial to evaluate the expression of 70 genes that are known to be involved in cellular death. This trial included 190 children diagnosed with ALL.

  • Overexpression of the BCL213 gene was associated with a reduced overall survival.
  • At 5 years, cancer-free survival was 85% for those with normal expression of BCL213, compared with only 66% for those with overexpression of BCL213.
  • Expression of the MCL1 and DAPK1 genes were associated with anticancer responses to prednisolone (a steroid commonly used in the treatment of ALL).
  • Expression of the BLC213, HRK, and TNF genes were associated with a resistance to treatment with L-asparaginase (agent commonly used in the treatment of ALL).

The researchers concluded that the expression of specific genes is associated with responses to certain therapeutic agents and overall survival in pediatric patients diagnosed with ALL. While further study is necessary to confirm these findings, these results add to a list of variables that further the individualization of therapy for these patients.

Reference: Holleman A, den Boer M, Menezes R, et al. The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia. Blood. 2006; 107; 769-776.

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