Title

Analysis of the CBFB, CBFA2 and AF-9 genes in familial acute myelogenous leukemia

Document Type

Article

Department

Haematology/Oncology

Abstract

The cloning of chromosomal translocation breakpoints from sporadic leukemias has identified genes that are implicated in the pathogenesis of acute myelogenous leukemia (AML). Although common, such chromosomal translocations are not necessary for the development of leukemias, suggesting that other underlying genetic factors are involved in the early stages of leukemia development. Familial AML is extremely rare, and families with the disease provide a unique resource for the study of the genes involved in the initial stages of cancer development. We investigate a single family in which several members have developed AML. Three members (a mother and two offspring) are affected with AML M4eo, and a third offspring is affected with AML M2. The average age of onset in the children (7 years) is significantly lower than that for the mother (30 years). Transmission of the disease seems to be in an autosomal-dominant manner. The small size of the pedigree reduces the power of genome-wide linkage analysis and therefore we used a candidate gene approach. Initially three genes were selected for analysis based on their reported involvement in familial and sporadic AML: CBFA2, CBFB and AF9. We performed genotyping at these loci to identify shared haplotypes between affected individuals. We will also report the results of direct mutation analysis of the candidate genes.

Comments

This work was published before the author joined Aga Khan University

Publication

Nature Genetics

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