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Four aged siblings with B cell chronic lymphocytic leukemia
F Fernhout1, R B Dinkelaar, A Hagemeijer
1Department of Clinical Chemistry, Lorentz Hospital Zeist, The Netherlands.
Insights
This study investigated four elderly siblings with B cell chronic lymphocytic leukemia (B-CLL), finding six distinct B-CLL cases and biclonality in two patients. The family shows high susceptibility to B-CLL, with CD8 expression noted in two cases.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Familial clustering of B cell chronic lymphocytic leukemia (B-CLL) is rare.
- Understanding the genetic and immunological basis of B-CLL in families is crucial for identifying susceptibility factors.
Purpose of the Study:
- To investigate the immunological and genetic characteristics of B-CLL in four elderly siblings.
- To determine if common factors contribute to B-CLL development within this family.
- To explore the significance of biclonality and CD8 expression in B-CLL.
Main Methods:
- Immunological marker analysis.
- Southern blot analysis of immunoglobulin (Ig) genes.
- Cytogenetic studies.
Main Results:
- All four siblings were diagnosed with B-CLL, with evidence of six distinct B-CLL cases identified through combined analyses.
- Two patients exhibited biclonal Ig gene rearrangement and cytogenetic aberrations, indicating two independent B-CLL clones.
- CD8 antigen expression was observed on B-CLL cells in the two oldest patients, a rare finding not associated with aggressive disease in this cohort.
Conclusions:
- The family demonstrates a high susceptibility to developing B-CLL, although a specific common causative factor remains unidentified.
- The presence of multiple B-CLL clones (biclonality) and CD8 expression can occur in B-CLL without necessarily indicating a more aggressive clinical course.
- This case series highlights the complexity of B-CLL development and suggests potential genetic predispositions within families.
Abstract:
All four aged siblings (>80 years) of one family presented with B cell chronic lymphocytic leukemia (B-CLL). In an attempt to find common characteristics in the four patients, we performed detailed immunological marker analysis, Southern blot analysis of immunoglobulin (Ig) genes, and cytogenetic studies. In three patients clonality of the B-cells could be proven by single Ig light chain expression, but in the fourth patient no Ig light chain expression was detected and clonality of the B cells could only be demonstrated by Southern blot analysis of the Ig genes. Interestingly, in two patients, the Ig gene rearrangement patterns were compatible with the presence of two independent B cell clones, whereas in the two other siblings a monoclonal rearrangement pattern was found. All four patients showed clonal chromosome aberrations, which were different in each patient. In the two patients with biclonal Ig gene rearrangement patterns, two unrelated clones could also be demonstrated by the cytogenetic studies. These combined Ig gene and cytogenetic data indicate the presence of two different B-CLL in two of the four patients. Remarkably, the B-CLL cells of the two oldest patients expressed the CD8 antigen, which is rarely observed. Our finding of six different B-CLL in the four living siblings indicates that the members of this family are highly susceptible to the development of B-CLL. However we could not identify a common factor to explain this susceptibility further. In contrast to the literature, the occurrence of two B-CLL in one patient and the expression of CD8 were not associated with clinically aggressive disease in this family.