Paquette, Gregory [Faculty advisor, College of Environment and Life Sciences]
Leukemia, Genetic translocations, Rhode Island Hospital
Hematological neoplasms, more commonly known as blood cancers, pose great concern within the United States healthcare system. These cancers originate within the bone marrow or lymphatic tissue and progress into the circulatory system. Hematological neoplasms are a result of genetic mutations in which the normal cell growth cycle is ex-changed for the uncontrollable growth of malignant cells. According to the Leukemia and Lymphoma Society, blood cancers accounted for 9.5 percent of all cancer related deaths in 2009. Every four minutes, a new patient is diagnosed with blood cancer and every ten minutes, someone dies from this malignancy. Research and development within the med-ical technology field has expanded knowledge of these neoplasms, allowing for accurate diagnosis and increased prognosis and treatment for patients.
Acute Promyelocytic Leukemia (APL) is a malignancy of the bone marrow in which the myeloid cell line is arrested at the promyelocytic division stage and therefore the cell line is unable to differentiate and produce mature, functional cells. The definitive characteristic of APL is a balanced reciprocal translocation between chromosome 15 and 17, or t(15:17). The retinoic acid receptor alpha gene, RARα, on the 17q12 chromosome fuses with the nuclear regulatory factor on the 15q22 chromosome, also known as the promyelocytic leukemia (PML) gene, to form a PML-RARα gene fusion product.
APL was first identified as being its own entity from other leukemias in 1957. Up until the early 1990’s, APL was treated with chemotherapeutic agents, but the remission rate of survival remained poor. Fairly recent development of a new treatment with al-trans retinoic acid, or ATRA, a derivative of vitamin A, has shown an almost complete remission rate in patients with APL. For those patients in which ATRA fails, ATO, or arsenic trioxide is used synergistically with ATRA to improve remission. If treated im-mediately, the complete remission rate of these patients is 95%, allowing for a normal quality of life to which everyone deserves.
For my Honors project, I first investigated the clinical, hematological and genetic findings behind APL. I then addressed the mechanism of action behind the various treat-ments available for patients with Acute Promyelocytic Leukemia to determine their effi-cacy. Lastly, I investigated a case study from a known patient with APL at Rhode Island Hospital under the direction of the Special Hematology Laboratory, in hopes for a better understanding of this rapidly, progressive hematological neoplasm.