Files

Download

Download Full Text (205 KB)

Abstract

Acute lymphocytic leukemia (ALL) is a blood disorder characterized by aberrant proliferation of immature lymphocytes. ALL is the most common cancer in children and can result from external influences, such as radiation, or internal influences, such as genetic mutation. Additionally, Ca2+/calmodulin-dependent kinase II (CaMK-II) is a serine/threonine protein kinase whose increased expression has been found in various leukemias. Zebrafish and human immune cells are analogous and both species have conserved hematopoietic stem cell specification mechanisms. In this study, the constitutively active form of CaMK-II, resulting from a threonine to aspartic acid point mutation at the 287 base-pair location (T287D), was paired with the EGFP transgene using Tol2 Gateway technology and injected into zebrafish at the one-cell stage. The zebrafish expressing the transgene were outcrossed to wild type and mutant p53 zebrafish and then monitored for leukemic development using flow cytometry and pathology. Based on FACS results, the mutant p53 bearing the T287D mutation were found to have increased levels of lymphocytes compared to the mutant p53 zebrafish without the T287D mutation. Furthermore, hematologists confirmed the development of B-cell leukemia/lymphoma from histological slides prepared from the mutant p53 with the T287D mutation. The mutant p53 without the T287D mutation did not yield such results. These findings highlight a potential role of CaMK-II in the abnormal development of lymphocytes and provide a useful model, from which, drug studies can be performed for potential treatment options.

Publication Date

2017

Current Academic Year

Senior

Faculty Advisor/Mentor

Dr. Robert Tombes

Faculty Advisor/Mentor

Dr. Sarah Rothschild

Rights

© The Author(s)

The Role of CaMK-II in the Development of Leukemia/Lymphoma in Danio Rerio

Share

COinS