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A clinicopathologic study of familial chronic lymphocytic leukemia
A R Shah1, K Maeda, M J Deegan
1Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202.
Insights
Three siblings developed chronic lymphocytic leukemia (CLL), with two alive and exhibiting distinct B-cell characteristics and gene rearrangements. This suggests potential evolution of different CLL clones within the same family.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Familial chronic lymphocytic leukemia (CLL) occurrence was investigated.
- Morphologic, immunophenotypic, cytogenetic, and immunoglobulin gene rearrangement analyses were employed.
- Three of six siblings were diagnosed with CLL.
Observation:
- Patient 1, diagnosed with Stage IV CLL, died after 9 years.
- Patients 2 and 3, diagnosed with Stage I and Stage O CLL respectively, are alive.
- Bone marrow analysis revealed mature lymphocytes in both patients, with different cellularity and patterns.
Findings:
- Patients 2 and 3 had normal karyotypes.
- Immunophenotyping showed distinct B-cell populations: patient 3 had minimal surface immunoglobulin expression, while patient 2 expressed IgM, IgD, and Kappa light chains.
- Gene rearrangement studies revealed different heavy chain rearrangement patterns in patients 2 and 3.
Implications:
- The distinct immunophenotypic and genotypic profiles suggest the evolution of two different chronic lymphocytic leukemia clones within this family.
- Understanding familial CLL heterogeneity is crucial for targeted therapies.
- Further research into the genetic underpinnings of familial CLL is warranted.
Abstract:
The familial occurrence of chronic lymphocytic leukemia was studied using morphologic, immunophenotypic, cytogenetic, and immunoglobulin gene rearrangement analyses. Three of six siblings developed chronic lymphocytic leukemia. One (patient 1) died 9 years after the diagnosis of chronic lymphocytic leukemia at age 67 years. The other two patients, ages 64 and 68 years (patients 2 and 3, respectively), are alive after chronic lymphocytic leukemia was diagnosed 11 and 4 years ago, respectively. Using the Rye classification, patient 2 and patient 3 had Stage I and Stage O disease, respectively. In contrast, patient 1 had Stage IV disease. The bone marrow of patient 2 was 90% cellular, with sheets of mature lymphocytes, and that of patient 3 was 70% cellular, with a nodular pattern of similar cells. Both patients 2 and 3 had normal karyotypes. Immunophenotyping studies revealed that patient 3 had an expanded population of B cells with minimal to no detectable expression of surface immunoglobulins and membrane-bound light chains. In contrast, the B-cell population of patient 2 expressed immunoglobulins M, D, and Kappa light chains. Gene rearrangement studies performed on these two patients revealed different but distinct patterns of heavy chain rearrangement. This may represent an evolution of two different clones of chronic lymphocytic leukemia in this family.