3p21 is a recurrent breakpoint in MDS/AML and t-MDS/t-AML suggesting, 3p21 site is likely to contain a gene (genes) involved in the pathogenesis of t(3;4)(p21;q34). Frequent deletion or allelic loss of band 3p21 is common in solid tumors, indicating the presence of tumor suppressor genes on this chromosome arm. The association among structural chromosome 3 aberrations and fragile sites on 3p may indicate the importance of previous mutagen exposure in the etiology of these diseases.
Although several cancer-related genes have been located to 3p21, no gene has yet been identified to be related with hematological malignancies. One of the candidate genes may be the AF3p21 gene, a novel fusion partner of the MLL gene described in a patient who had developed therapy-related leukemia with t(3;11)(p21;q23). AF3p21 encodes a protein localized exclusively in the cell nucleus, suggesting the possibility that AF3p21 protein plays a role in signal transduction in the nucleus.