Identification of differentially expressed genes in large granular lymphocyte leukemia

Abstract

Large granular lymphocyte (LGL) leukemia is a human lymphoproliferative disorder associated with autoimmune disease. The etiology of LGL leukemia is not known. It is conceivable that antigen activation plus lymphokine secretion lead to leukemic LGL proliferation. To understand more about the molecular mechanisms involved in the pathogenesis of LGL leukemia, we decided to investigate differentially expressed genes in leukemic LGL. By using microarray, a novel technique, we have identified a number of differentially expressed genes. The most predominantly expressed genes such as granzyme H, granzyme B, perforin, and lymphopain are all involved in the cytotoxic function of activated NK and T cells. Phosphatase in activated cells (PAC-1) is also constitutively expressed in leukemic LGL. PAC-1 is a mitogen induced dual specific Thr/Tyr phosphatase with stringent substrate specificity for MAP kinases. The role of the above mentioned constitutively expressed genes in relation to pathogenesis of LGL leukemia will be further investigated.