Chronic Lymphocytic Leukemia FISH Probes
Deletions in the long arm of chromosome 6 occur in about 6% of CLL, most frequently in the 6q21 region. Studies show that 6q loss is often an early step in CLL development, and triggers gene pathways that lead to the accumulation of additional genetic changes.
Chromosome 11q deletions can be found in about 10% of early stage and 25% of advanced CLL. The ATM gene, which encodes a DNA damage response kinase, is found in the 11q23 region often lost in these deletions.
Overexpression of the BCL2 protein is ubiquitous in CLL, and is usually caused by loss of microRNA-mediated repression of BCL2 gene expression. Amplified BCL2 results in extended survival of pre-malignant B lymphocytes, contributing directly to disease development.
In CLL, 11q deletions can vary substantially in size. BIRC3 is found in one of the larger, more commonly deleted regions. BIRC3 copy number variations are rarely detected early on in CLL, and instead tend to arise over the course of disease progression.
Deletions in the long arm of chromosome 13 are among the most common genetic aberrations in CLL. Commonly deleted regions have been shown to house the D13S319 locus (lost in 10-29% of cases) and the LAMP1 gene at 13q34 (indicated by some studies to be deleted in up to 4% of patients).
Wildtype MDM2 aids in degradations of the ubiquitous tumor suppressor p53. Mutations in the gene, therefore, can negatively impact p53's disease-suppressing abilities. MDM2 has been found overexpressed in 64-73% of CLL cases.
MYB encodes a transcription factor that helps regulate normal B-lymphoid development. Production of the protein is supposed to phase out as the cells develop, but aberrant expression can lead to abnormal B-cell development, and, consequently, lymphoproliferative disorders like CLL.
RB1 helps regulate genome stability by monitoring G1 to S phase. The gene can be lost during 13q14 deletion, one of the most common genetic abnormalities detected in CLL.
TP53 is a well-established tumor suppressor that helps regulate DNA damage response. Abnormalities in the gene, most often deletions, occur in around 10-15% of CLL patients. More than 80% of patients with 17p deletion also carry TP53 mutations in the remaining allele.