Genetics in Hematologic Disease
Hematologic diseases that result in bone marrow failure or leukemia are both common yet extremely complex diseases.
While some diseases on bone marrow and blood, like myelodysplastic syndrome (MDS), can manifest as anemias manageable for a time with transfusions, others can be life threatening. One of the more devastating and difficult to treat is Acute Myelogenous Leukemia (AML) with approximately 21,000 new cases in 2017 in adults and children in the United States alone. While standard chemotherapy and bone marrow transplantation help some AML patients, the majority of patients die from their disease. In fact, the treatments for AML have changed very little in the past 30 years.
All cancers are caused by genetic changes, mutations, in cells. These changes are not passed down in families but rather occur in specific cells in our body such as the bone marrow. These genetic changes accumulate over time and some give cells a competitive growth advantage over their neighboring cells that have no new mutations.
Cells get their competitive growth advantage by mutations that change patterns of gene expression and DNA replication. In AML and MDS, some of these altered patterns of gene expression are the consequence of mutations in genes that control gene expression epigenetically, that is, they influence the chemical modification of proteins, RNA or DNA without changing the fundamental DNA sequence of genes within the cell. Therapies that modulate epigenetic factors offer the possibility of restoring normal gene expression or targeting only mutated cells. Epigenetic-based therapies are leading a new wave of medicines for AML and MDS.