Home
HelpTest ID: BCLL IGH Somatic Hypermutation Analysis, B-Cell Chronic Lymphocytic Leukemia (B-CLL), Varies
Useful For
Providing prognostic information in patients with newly diagnosed B-cell chronic lymphocytic leukemia
This test is not intended for use in providing prognostic information for patient with other B-cell neoplasms or hematopoietic tumors.
Special Instructions
Reporting Name
IGH Somatic Hypermutation in B-CLLSpecimen Type
VariesShipping Instructions
1. Both refrigerated and ambient specimens must arrive within 7 days of collection.
2. Collect and package specimen as close to shipping time as possible.
Necessary Information
1. Molecular Hematopathology Patient Information is required.. Testing may proceed without the patient information; however, it aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.
2. If form is not provided, include the following information with the test request: specimen source, pertinent clinical history (ie, complete blood cell count results and relevant clinical notes), and clinical or morphologic suspicion.
Specimen Required
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 4 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
3. Label specimen as blood.
Specimen Stability: Refrigerated/Ambient
Specimen Type: Bone marrow
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD)
Specimen Volume: 2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Send bone marrow specimen in original tube. Do not aliquot.
3. Label specimen as bone marrow.
Specimen Stability: Refrigerated/Ambient
Specimen Type: Extracted DNA from blood or bone marrow
Container/Tube: 1.5- to 2-mL screw-top tube
Specimen Volume: Entire specimen
Collection Instructions:
1. Label specimen as extracted DNA and indicate specimen source (blood or bone marrow).
2. The required volume of DNA is 50 mcL at a concentration of 20 ng/mcL.
3. Include volume and concentration on tube.
Specimen Stability: Frozen (preferred)/Refrigerated
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | 7 days |
Clinical Information
During early B-cell development, IGH genes are assembled from multiple polymorphic gene segments that undergo rearrangements and selection, generating variable diversity joining (VDJ) combinations that are unique in both length and sequence for each B cell. In addition, newly acquired (somatic) point variations are introduced into the variable (V) regions of mature B cells during the germinal center reaction in lymph nodes in a process called somatic hypermutation (SHM). Since chronic lymphocytic leukemia (CLL) originates from the malignant transformation of single lymphoid cells, each daughter cell shares one or, sometimes, more unique "clonal" antigen receptor gene rearrangements, which are cell and tumor specific (ie, a tumor cell "fingerprint"). Clonal IGHV gene hypermutation status provides important prognostic information for patients with CLL and small lymphocytic lymphoma (SLL). The presence of IGH SHM is defined as greater than 2% difference from the germline VH gene sequence identity (mutated), whereas less than or equal to 2% difference is considered no SHM (unmutated). The status of SHM has clear influence on the median survival of CLL patients. Hypermutation of the IGH variable region is strongly predictive of a good prognosis, while lack of variants predicts a poorer prognosis.
Reference Values
An interpretive report will be provided.
Interpretation
The presence or absence of somatic hypermutation (SHM) in the immunoglobulin heavy chain gene (IGH) variable (V) region DNA will be reported. A variation frequency of greater than 2% will be reported as mutated. Both the percent mutation and the V region allele identified in the rearrangement will be included in the report.
B-cell chronic lymphocytic leukemia (B-CLL) lacking SHM of the IGH V region (unmutated) is associated with a significantly worse prognosis than B-CLL containing SHM of the IGH V region (mutated).
Clinical Reference
1. Davi F, Langerak AW, de Septenville AL, et al. Immunoglobulin gene analysis in chronic lymphocytic leukemia in the era of next generation sequencing. Leukemia. 2020;34(10):2545-2551. doi:10.1038/s41375-020-0923-9
2. Agathangelidis A, Sutton LA, Hadzidimitriou A, et al. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: From patient material to sequence interpretation. J Vis Exp. 2018;(141):10.3791/57787. Published 2018 Nov 26. doi:10.3791/57787
3. Rosenquist R, Ghia P, Hadzidimitriou A, et al. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations. Leukemia. 2017;31(7):1477-1481. doi:10.1038/leu.2017.125
Day(s) Performed
Monday, Wednesday, Friday
Report Available
14 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81263-IGH (immunoglobulin heavy chain locus) (eg, leukemia and lymphoma, B-cell), variable region somatic mutation analysis
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| BCLL | IGH Somatic Hypermutation in B-CLL | 50627-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 39465 | BCLL Result | No LOINC Needed |
| MP005 | Specimen Type | 31208-2 |
| 19674 | Final Diagnosis | 50398-7 |
Method Name
Polymerase Chain Reaction (PCR) and Next-Generation Sequencing (NGS)
Specimen Minimum Volume
Blood/Bone marrow: 1 mL
Extracted DNA: see Specimen Required
Forms
1. Molecular Hematopathology Patient Information is required.
2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
mml-benign-hematology-disorders, mml-lymphoma, mml-lymphoma