AML poor prognosis factor, TPD52, is associated with the maintenance of haematopoietic stem cells through regulation of cell proliferation

Abstract

Acute myeloid leukaemia (AML) is a blood cancer where undifferentiated myeloid cells are increased in the bone marrow and peripheral blood. As AML is dangerous and shows poor prognosis, many researchers categorised the relevant cytogenetic factors according to risk and prognosis. However, the specific reasons for poor cytogenetic factors remain unknown. We analysed a large data set from AML patients and found that TPD52 expression is elevated in patient groups with poor cytogenetic factors. As the amino acid sequence of TPD52 is evolutionally conserved in vertebrates, zebrafish embryos were used to investigate the function of TPD52. Since myeloid-biased haematopoietic stem cells (HSCs) are relevant to AML, the function of TPD52 in the development of HSCs was investigated. We determined that the zebrafish paralog, tpd52, is important for the maintenance of HSCs through regulation of cell proliferation. As tpd52 is linked to cell proliferation in zebrafish embryos, the proliferation-related gene, CD59, was correlated to TPD52 in every AML cohort with a high correlation coefficient. We suggest that TPD52 can be a novel therapeutic target for AML patients with poor cytogenetic factors. Additionally, more studies between TPD52 and CD59 will further increase the value of TPD52 as a novel target.