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Familial chronic lymphocytic leukemia in Norway and Denmark. Comments on pleiotropy and birth order
Viggo Jønsson1, Geir E Tjønnfjord, Tom B Johannesen
1Hematology Department, Oslo University Hospital Aker, Faculty Division, 235 Trondheimsvei, NO 0514 Oslo, Norway. viggo.jonsson@medisin.uio.no
Insights
Genomic imprinting may explain non-Mendelian inheritance patterns in chronic lymphocytic leukemia (CLL). Paternal transmission of CLL predominantly affects younger sons, while maternal transmission shows no birth order preference.
Area of Science:
- Hematology
- Genetics
- Oncology
Background:
- Chronic lymphocytic leukemia (CLL) exhibits complex inheritance patterns.
- Familial clustering suggests a genetic component, but classical Mendelian inheritance is not always observed.
Purpose of the Study:
- To investigate the genetic basis of chronic lymphocytic leukemia (CLL).
- To explore non-Mendelian inheritance patterns in familial CLL cases.
Main Methods:
- Ascertainment of 51 families and 141 cases from 800 CLL patients with other hematological malignancies.
- Analysis of disease transmission patterns using matrix conjugation and Cox regression.
- Comparison of B-cell expression in familial versus sporadic CLL.
Main Results:
- Paternal CLL transmission was significantly higher in younger sons (RR=3.25) compared to maternal transmission (RR=1.47).
- Maternal CLL transmission showed equal distribution among siblings regardless of birth order.
- B-cell expression was similar in familial and sporadic CLL, suggesting genetic factors influence disease susceptibility rather than cell-surface markers.
Conclusions:
- Parental genomic imprinting is a potential mechanism explaining the observed non-Mendelian inheritance in CLL.
- These findings highlight the role of epigenetic modifications in CLL familial aggregation.
Aim:
To investigate the genetics of chronic lymphocytic leukemia (CLL).
Materials And Methods:
In 56 (7%) out of 800 CLL patients with concomitant malignant hematological disease, 51 families and 141 cases were ascertained.
Result:
106 cases (75%) of CLL, 27 cases (19%) of nonCLL and 8 cases (6%) of myeloproliferative disorders. Paternal disease was transmitted primarily to the youngest sons in the sibship while maternal disease was transmitted equally to all sibs, demonstrated by means of matrix conjugation and confirmed with Cox regression on parity and birth order (maternal-offspring combination: relative risk (RR), 95% confidence interval (CI)=1.47 (0.89 - 2.43), p=0.12, compared with paternal-offspring combination: RR=3.25, 95% CI=(1.57-6.72), p<0.001). The B-cell expression in familial and sporadic CLL was indistinguishable.
Conclusion:
Parental genomic imprinting is pointed out as one possible mechanism behind this non-Mendelian genomic output.
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