Inheritance of Susceptibility to Malignant Blood Disorders

Viggo Jønsson,Gudrid Andosdottir,Bjarni Á Steig,Neil D Jones,Haneef Awan,Geir E Tjønnfjord,Tom B Johannesen

doi:10.1038/s41598-019-38879-y

Abstract

Malignant blood disorders depend on heritable susceptibility genes and occur in familial aggregations. We suggest a model of transgenerational segregation of the susceptibility genes based on the study of malignant blood disorders in Norwegian and Danish families with unrelated parents, and in the inbred Faroese population with related parents. This model, consisting of parental genomic imprinting and mother-son microchimerism, can explain the male predominance in most of the diseases, the predominance of affected parent-offspring when parents are not related, and the different modes of segregation in males and females. The model displays a specific pattern in the distribution of affected relatives for each diagnosis, viz. a characteristic distribution in the pedigrees of family members with malignant blood disorder related to the proband. Three such patterns, each reflecting a specific transgenerational passage, were identified: (1) alterations in the number of affected relatives in paternal lines alone, e.g. in patterns for probands with multiple myeloma; (2) alterations in the number of affected relatives in both paternal and maternal lines for probands with chronic lymphocytic leukemia; and (3) no alterations in the numbers of male and female affected relatives in the parental lines, e.g. for probands with some types of malignant lymphoma.

Highlights

Strong evidence supports the notion that leukemia, lymphoma, myeloma and other malignant blood disorders (MBD) in man constitute an entity of heritable diseases1–7, but the transgenerational transfer of the susceptibility to MBD is still largely unknown
The myeloproliferative disorders are more frequent in the Faroe material (28% of all MBD) than in the families from Norway and Denmark (8%). (Table 1) acute myelogenous leukemia (AML) is predominant but with a frequency lower than expected when comparing with the percentage of AML reported by the whole-population Norwegian and Danish Cancer Registries (P < 0.05)
The percentage of MM is increased on the Faroe Islands (P < 0.01) where MM is as common as chronic lymphocytic leukemia (CLL)

Summary

Introduction

Strong evidence supports the notion that leukemia, lymphoma, myeloma and other malignant blood disorders (MBD) in man constitute an entity of heritable diseases1–7, but the transgenerational transfer of the susceptibility to MBD is still largely unknown. The MBD-patients observed in the Faroese family and in MBD-families from Norway and Denmark were compared with “a normal material” based on data from the whole population National Cancer Registries in Oslo34 and Copenhagen35, and from the LYFO-Registry36 (Table 1).

Results

Conclusion