Evidence of immune disruption up to 9.8 years prior to diagnosis of chronic lymphocytic leukaemia: A prospective study

Researchers at the National Cancer Institute may have uncovered a possible early cause of chronic lymphocytic leukemia (CLL), according to a prospective study that involved more than 77,000 patients, presented at AACR 2009, Denver.

“Although CLL can be a devastating disease, we know little about what causes it, except that it is linked with family history and aging,” said Dr Neil Caporaso a section chief of the genetic epidemiology branch at the National Cancer Institute. Drawing on data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which included 77,469 healthy individuals, Caporaso and colleagues may have identified an early immune disruption that could lead to CLL.

Caporaso and colleagues identified 109 patients in the database that had a diagnosis of CLL; the diagnosis occurred at a median age of 70 years and 61 percent of the patients were male. These patients had serum available for analysis collected years prior to the diagnosis of CLL. Researchers assessed for the immune measures found in M-proteins and kappa-lambda free light chains. Researchers assessed the serum tests conducted two to almost ten years prior to diagnosis of CLL.

They found that 31 percent of patients who eventually developed CLL had a skewed kappa-lambda free light chain ratio, which Caporaso said is evidence of an early immune disruption. In one patient, this disruption was noted 9.8 years prior to diagnosis. By contrast, hypogammaglobulinemia-an indication of impaired immune function that is common in CLL-was found in only 13.1 percent of patients and was not present in any patients until three years prior to diagnosis. “It’s possible that these disruptions in the kappa-lambda ratio indicate early abnormal clone (collection of similar cells) that lead to CLL,” said Caporaso. “Our aim is to better understand them in order to unravel the cause of this puzzling and common blood cancer.”