The Role of NOTCH1, GATA3, and c-MYC in T Cell Non-Hodgkin Lymphomas

SIMPLE SUMMARY: Peripheral T cell lymphomas (PTCLs) comprise 10–15% of all non-Hodgkin lymphomas, and are more aggressive with worse prognosis. Due to their rarity and significant molecular abnormalities, the pathogenesis of PTCLs is not well understood. The expressions of NOTCH1, GATA3, and c-MYC have been linked to a poorer prognosis in PTCL, and are implicated in downstream processes. The aims of this review are to elucidate the role of NOTCH1, GATA3, and c-MYC in patients with PTCLs to provide additional information about the disease’s pathogenesis and to investigate the master regulator between these genes that will provide a basis for new therapeutic strategies and improve PTCL patients’ survival rates. NOTCH1 greatly influences the progression, pathogenicity, and development of PTCLs. Because NOTCH signalling does not rely on enzymatic signal amplification, and all Notch ligands and receptors include extracellular domains that are essential for receptor binding and activation, making them accessible to circulating therapies and targeting for different therapeutic strategies. ABSTRACT: Lymphomas are heterogeneous malignant tumours of white blood cells characterised by the aberrant proliferation of mature lymphoid cells or their precursors. Lymphomas are classified into main types depending on the histopathologic evidence of biopsy taken from an enlarged lymph node, progress stages, treatment strategies, and outcomes: Hodgkin and non-Hodgkin lymphoma (NHL). Moreover, lymphomas can be further divided into subtypes depending on the cell origin, and immunophenotypic and genetic aberrations. Many factors play vital roles in the progression, pathogenicity, incidence, and mortality rate of lymphomas. Among NHLs, peripheral T cell lymphomas (PTCLs) are rare lymphoid malignancies, that have various cellular morphology and genetic mutations. The clinical presentations are usually observed at the advanced stage of the disease. Many recent studies have reported that the expressions of NOTCH1, GATA3, and c-MYC are associated with poorer prognosis in PTCL and are involved in downstream activities. However, questions have been raised about the pathological relationship between these factors in PTCLs. Therefore, in this review, we investigate the role and relationship of the NOTCH1 pathway, transcriptional factor GATA3 and proto-oncogene c-MYC in normal T cell development and malignant PTCL subtypes.