A sensitive diagnostic test for the detection of mutations in chronic lyphocytic leukemia

A sensitive diagnostic test for the detection of mutations in chronic lyphocytic leukemia


Recently a research group at the NIH in collaboration with NeoGenomics Lab in California developed a sensitive diagnostic method for the detection of multiclonal mutations in patients with chronic lymphocytic leukemia (CLL) that were treated with Bruton’s tyrosine kinase (BTK) inhibitors.

Patients with CLL that develop resistance to BTK inhibitors are typically positive for mutations in BTK or phospholipase c gamma 2 (PLCγ2). BTK mutations present at the C481S mutation hotspot are known to alter the active site of the mutant BTK. This mutant binds Ibrutinib in a reversible manner.

To better understand the development of resistance mechanisms in patients with CLL, Albitar and others developed a high sensitivity (HS) mutation assay using bridged nucleic acids (BNAs). The very sensitive assay was used in combination with Sanger sequencing and next generation sequencing (NGS) to test cellular DNA and cell free DNA (cf-DNA) from patients with CLL.

The results of this assay suggested that ibrutinib-naïve patients with CLL do not have BTK or PLCγ2 mutations. The researchers suggested that assaying cfDNA using this method may allow detection of mutations much earlier as compared with assaying cellular DNA. This may allow assaying for these mutations in patients with lymphoma that have only a few circulating lymphoma cells.

What is chronic lymphocytic leukemia?

Chronic lymphocytic leukemia
 (CLL) is a type of cancer that starts from cells develop into a type of 
white blood cells called lymphocytes in the bone marrow. The cancer (leukemia) cells originate in the bone marrow but then migrate into the blood. In CLL, leukemia cells often develop slowly over time. Many people don't have any symptoms for at least a few years. However, in time, the cancer cells can spread to other parts of the body, including the lymph nodes, liver, and spleen

Links to the publications and BTK inhibitors



BTK inhibitors

Ibrutinib -  https://en.wikipedia.org/wiki/Ibrutinib                                            

Acalabrutinib  -  https://en.wikipedia.org/wiki/Acalabrutinib 

BTK inhibitor review  -