Genetics in Hematologic Neoplasia

Hematologic diseases that result in bone marrow failure or leukemia are both common yet extremely complex diseases.

While some diseases, like myelodysplastic syndrome (MDS), can manifest as anemias manageable with transfusions, others can be life threatening. One of the most devastating and difficult to treat is acute myelogenous leukemia (AML) with approximately 19,000 new cases in 2014 in adults and children in the United States alone. While standard chemotherapy and bone marrow transplantation help some AML patients, the majority of patients are not cured of their disease. In fact, the treatment for AML has changed very little in more than 30 years.

All cancers are caused by genetic changes in our cells. Most of those 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 mutations.

Cells get their competitive growth advantage by mutations that change gene expression patterns. In AML and MDS, some of these altered patterns of gene expression come from mutations in genes that control gene expression epigenetically, that is, they influence the proteins surrounding the genes within the cell. Therapies that exploit epigenetics offer the possibility of restoring normal gene expression or targeting only sick cells with fewer side effects than standard chemotherapies. Epigenetic-based therapies are leading a new wave of medicines for AML and MDS.

Hematologic Neoplasia