Interpretive Handbook

Test 83089 :
Chronic Lymphocytic Leukemia (CLL), FISH

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Chronic lymphocytic leukemia (CLL) is the most common leukemia in North America. The most common cytogenetic abnormalities in CLL involve chromosomes 6, 11, 12, 13, and 17. These are detected and quantified using the CLL FISH panel. Use of CpG-oligonucleotide mitogen will identify an abnormal CLL karyotype in at least 80% of cases (CPG / Chromosome Analysis, CpG Mitogen Study for B-Cell Disorder). Unstimulated conventional chromosome studies are usually not successful for CLL (BM / Chromosome Analysis, Hematologic Disorders, Bone Marrow and HBL / Chromosome Analysis, Hematologic Disorders, Blood). 


This FISH test detects an abnormal clone in approximately 70% of patients with indolent disease and >80% of patients who require treatment. At least 5% of patients referred for CLL FISH testing have translocations involving the IgH locus; approximately 66% of these patients have translocations that result in fusion of IGH/CCND1, IGH/BCL2, or IGH/BCL3. Fusion of IGH and CCND1 is associated with t(11;14)(q13;q32), IGH and BCL2 with t(14;18)(q32;q21), and IGH and BCL3 with t(14;19)(q32;q13.3). Patients with t(11;14)(q13;q32) usually have the leukemic phase of mantle cell lymphoma. Patients with t(14;18)(q32;q21) or t(14;19)(q32;q13.3) may have an atypical form of B-CLL or the leukemic phase of a lymphoma.


The prognostic associations for chromosome abnormalities detected by this FISH assay are, from best to worst: 13q-, normal, +12, 6q-, 11q-, and 17p-.

Useful For Suggests clinical disorders or settings where the test may be helpful

Detecting a neoplastic clone associated with the common chromosome abnormalities seen in patients with chronic lymphocytic leukemia (CLL)


Identifying and tracking known chromosome abnormalities in patients with CLL and tracking response to therapy


Distinguishing patients with 11;14 translocations who have leukemic phase of mantle cell lymphoma from patients who have CLL 


Detecting patients with atypical CLL or other forms of lymphoma associated with translocations between IGH and BCL2, BCL3, MYC, or other partner genes

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe set.


The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Dewald GW, Brockman SR, Paternoster SF, et al: Chromosome anomalies detected by interphase FISH: correlation with significant biological features of B-cell chronic lymphocytic leukemia. Brit J Haematol 2003;121:287-295

2. Dohner H, Stilgenbauer S, Benner A, et al: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000 Dec;343(26):1910-1916

3. Van Dyke DL, Shanafelt TD, Call TG, et al: A comprehensive evaluation of the prognostic significance of 13q deletions in patients with B-chronic lymphocytic leukaemia. Br J Haematol 2010;148:544-550

4. Zent CS, Call TG, Hogan WJ, et al: Update on risk-stratified management for chronic lymphocytic leukemia. Leuk Lymphoma. 2006;47:1738-1746

5. Cavazzini F, Rizzotto L, Sofritti O, et al: Clonal evolution including 14q32/IGH translocations in chronic lymphocytic leukemia: analysis of clinicobiologic correlations in 105 patients. Leuk Lymphoma 2012;53:83-88