Use of Checkpoint Inhibitors in Gray Zone Lymphoma.

Checkpoint inhibitors, cancer immunotherapies, are the new forms of treatment for gray zone lymphoma, a rare subtype that combines the characteristics of both Hodgkin and non-Hodgkin disease forms. Programmed cell death protein 1/programmed cell death ligand 1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) modulate the immune system function. Immunological checkpoints can be stimulatory or inhibitory, and tumors can use these checkpoints to protect against immune system attacks.

Tissue methylation and demethylation influence translesion synthesis DNA polymerases (TLS) contributing to the genesis of chromosomal abnormalities in myelodysplastic syndrome.

Aims: DNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle.

Methods: We evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (, , , and ).

Proteins of the mitotic checkpoint and spindle are related to chromosomal instability and unfavourable prognosis in patients with myelodysplastic syndrome.

Aims: To study the immunoexpression of proteins related to the mitotic checkpoint (cell division cycle 20 (CDC20), mitotic arrest deficient 2 (MAD2)) and the mitotic spindle (Aurora-B) in patients with myelodysplastic syndrome (MDS).

Methods: Protein expression was analysed in bone marrow tissue samples from 40 patients with MDS using immunohistochemistry. Prognostic markers (transfusion dependency, depth of cytopenias, chromosomal abnormalities and survival) were also studied.