Meiotic Drive in Chronic Lymphocytic Leukemia compared with other Malignant Blood Disorders

Studies of families with two or more cases of malignant blood disorders (lympoproliferative and/or myeloproliferative) provide a description of the pathway of susceptibility down through the generations towards the proband. The united observations fit into a non-Mendelian operational model consisting of parental genomic imprinting combined with feto-maternal microchimerism. Male affected relatives of a proband are predominant in paternal lines with maternal imprinting, while female affected relatives are predominant in lines with maternal affiliation and paternal imprinting. The findings suggest the influence of a so-called polymorphic equilibrium with segregation distortion related to parental imprinting (fitness optimalization). In the generations before a proband, affected relatives with the same diagnosis may covariate, viz. be present with a higher frequency than expected (relative superiority); or contravariate, that is a lower frequency than expected (mutual minority). Covariation has been observed especially among affected relatives with multiple myeloma, diffuse large B-cell lymphoma, acute myeloid leukemia, Hodgkin’s lymphoma and some few other diagnoses. Contravariation is only seen among affected relatives with chronic lymphocytic leukemia. The dynamic drive of susceptibility in an affected family with birth order effect and/or anticipation is regarded as an additional polymorphic equilibrium with segregation distortion caused by feto-maternal microchimerism.