Molecular genetic features of cutaneous T-cell lymphomas development on example of mycosis fungoides and Sezary syndrome

Abstract

Cutaneous T-cell lymphomas are a heterogeneous group of T-cell lymphoproliferative diseases affecting the skin. Mycosis fungoides and Sezary syndrome are the most studied variants of them. The literature review includes the latest published data on the pathological processes development in mycosis fungoides and Sezary syndrome and the diagnosis of these diseases. The genomic instability features in cutaneous T-cell lymphomas are described, the existing hypotheses of the origin of these diseases are considered based on the results of T-cell receptor repertoire studying.

Role of cytokine in malignant T-cell metabolism and subsequent alternation in T-cell tumor microenvironment

“…Genetic alternation in these receptors invariably affects TCR-mediated signaling, TCR complex assembly formation, and the level of various proteins such as TCR-associated enzymes, along with various transcription factors. All these are important for the proper execution of downstream signaling mediated through these receptors ( 8 , 26 , 26 , 38 , 50 , 76 , 83 , 96 , 97 ). It has been found that enhanced TCR activation through gain-of-function mutation in the extracellular domain of CD28 and the translocation of CTLA4-CD28 occurred in CTCL ( 98 , 99 ).…”

“…The overexpression of downstream signaling components like MAPK of cytokine receptors is due to gain-of-function mutation in B-Raf (p. Asp594Asn) and ERK-1 (p. Glu322Ala, p. Glu322lys) in MF subjects (74). In stage IV subjects of MF, mutations were identified in KRAS (Kristen Rat Sarcoma Viral oncogene homolog) and NRAS (Neuroblastoma RAS Viral oncogene homolog) genes (74)(75)(76). Immunohistochemistry studies revealed that in the nucleus of 53% cells of MF lesion, ERK1/2 gets phosphorylated, which has been associated with phospho-4E-BP1 (Eukaryotic Translation Initiation Factor 4E Binding Protein 1) (p-4E-BP1) upregulation.…”