Chromosomal instability is a characteristic feature of myeloid malignancies and the preleukemic syndromes that predispose to these leukemias. My primary research interest is to elucidate the molecular basis for genomic instability in these diseases. We have accrued evidence that genomic instability in myeloid malignancies may be driven by a combination of ongoing constitutive DNA damage coupled with increased activity of the error-prone non homologous end-joining (NHEJ) pathway which results in improper repair of double strand breaks (DSB). This cycle of DNA damage and misrepair is driven by endogenous reactive oxygen species production, a likely source for genomic instability in myeloid leukemias and premalignant syndromes that introduces genomic changes into DNA and drives disease progression.
