Chronic Lymphocytic Leukemia/Lymphoma (CLL)


Chronic lymphocytic leukemia (CLL) is a malignancy of mature B lymphocytes and accounts for ~7% of all B-cell lymphomas and 40% of all adult leukemias.  The median age of diagnosis is 65 years of age and affects more males than females.  In CLL, mature clonal B lymphocytes accumulate in the blood, spleen and other lymphoid organs and is diagnosed when there are >5×109/L  B cells in the peripheral blood persisting for more than 3 months.  Clinical features at diagnosis can vary, from asymptomatic to fatigue, hemolytic anemia, splenomegaly, hepatomegaly or lymphadenopathy. Small lymphocytic lymphoma (SLL) is the nodal variant of CLL with little or no peripheral involvement.

Deletions of 17p usually include the TP53 locus and are identified in 5-10% of cases by FISH.  A subset of these cases will have a mutation in the other allele.  Deletions of 17p are associated with a poor prognosis in CLL.

Deletions of 11q usually include the ATM locus and are identified in 15-20% of cases by FISH. A substantial proportion of these cases will have a mutation in the other allele.  Deletions of 11q are associated with a poor prognosis in CLL.

Trisomy 12 is identified in 15% of cases by FISH. Some of the cases with trisomy 12 will also have translocations involving IGH and BCL2/3 or mutations within NOTCH1.  Trisomy 12 is associated with an intermediate prognosis.

Deletions of 13q can be variable in size. and are identified in 50% of cases by FISH.  Generally the deletion does not involve the RB1 locus and targets the 13q14 locus which contains non-coding RNAs thought to be important in gene regulation.  Both heterozygous and homozygous deletions of this region are identified and are associated with a good prognosis in CLL.


The CLL FISH panel is offered for patients with a confirmed diagnosis of CLL for prognostic purposes to aid in patient management and is not diagnostic of CLL.


  • Completed CGL Lymphoid Testing requisition form
  • One of the following specimens (see our Specimen Guidelines, Cytogenetics FISH test type):
    • 4 mL peripheral blood collected in sodium heparin tubes (green top)
    • 1×1.0 mL of marrow aspirate in 9mL media (RPMI 1640, 3.8% FBS, antibiotics)
  • NOTE:  FFPE tissue has NOT been validated for this assay and is therefore not an acceptable specimen type


Results are reported within fourteen days from receipt of specimen and completed requisition form.  


The result of the tested loci can be stratified according to increasing risk as follows: 13q deletion (sole abnormality), with relatively good prognosis; normal result or trisomy 12, with an intermediate prognosis; 11q deletion (ATM) and 17p deletion (TP53), with poor prognosis.

Up to 80% of CLL patients will have a cytogenetic abnormality detected by FISH using the standard four locus panel.  The remainder (20%) will have normal copy number at these loci, but may have undetectable cytogenetic abnormalities elsewhere.


The submitted specimen is harvested into a methanol-acetic acid (MAA) fixed cell pellet. The pellet is used to perform FISH analysis on interphase nuclei. Using a commercial kit manufactured by Vysis Inc., four loci are interrogated using probes which will identify copy number abnormalities of 11q22 (ATM), 13q14, 17p13 (TP53), and the centromere of chromosome 12.  This technique will confidently detect a clonal population (with a genetic alteration at one or more of the tested loci) only if it exceeds ~10% of the nucleated cells in the specimen.


  1. Dighiero G (2008)  Lancet PMID: 18358929
  2. Fabbri G  (2016)  Nat Rev Cancer PMID: 26911189
  3. Döhner H et al (2000) N Engl J Med. PMID: 11136261
  4. Van Dyke et al (2010) Br J Haematol (2010) PMID: 19895615