Aberrant DNA Methylation and Epigenetic Inactivation of hMSH2 Decrease Overall Survival of ALL Patients

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in childhood and adults. While the survival rate of ALL patients has been improved obviously, nearly one quarter of children with ALL will die (Gaynon, 2005). ALL in adults affects a comparatively young population and has proved to be refractory, with the 5-year survival rate of around 40% (Plasschaert et al., 2004). ALL originates from malignant transformation of lymphocyte progenitor cells into leukemic cells of the B-cell and T-cell lineages (Pui et al., 2011). However, one of the known genetic aberrations in ALL are insufficient to induce this disease (Pui et al., 2004), suggesting that there are other genetic or epigenetic alterations in the leukemic transformation. Mismatch repair (MMR) system is involved in the DNA damage recognition and repair. Human mutS homolog 2 (hMSH2) functions as a core MMR protein and usually forms hetero-dimmers with protein homologs hMSH3 or hMSH6 (Fishel, 2001). The hetero-dimmer is