ABSTRACT
Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are severe chronic inflammatory joint diseases with different immune-mediated mechanisms playing a role in their pathogenesis. Rheumatoid arthritis is an erosive arthritis of peripheral joints and AS is a spondyloarthropathy affecting mainly sacroiliac and spinal joints leading to excessive bone formation and ankylosis. The coexistence of RA and AS in the same patient is rare. Presented here is a 52-year-old patient with long-standing AS with bilateral ankylosis of sacroiliac joints who developed peripheral symmetric polyarthritis while being treated with the interleukin 17 inhibitor secukinumab introduced due to secondary inefficacy of the tumor necrosis a inhibitor etanercept. He was finally diagnosed with seropositive RA coexisting with AS and treatment was changed to the Janus kinase inhibitor tofacitinib. Eventually, remission was sustained with use of the interleukin 6 inhibitor tocilizumab. This is the first case of RA developing during anti-interleukin 17 therapy. Although tocilizumab lacks efficaciousness in AS, in this case therapy was succesful as the RA-driving cytokine mechanism possibly prevailed.
ABSTRACT
RATIONALE: A prolonged, prodromal phase before definitive paediatric precursor B acute lymphoblastic leukaemia (BCP ALL) diagnosis is rarely observed. PATIENTS CONCERNS: In the first, the patient presented with an aplastic preleukemic phase, whilst the second presented with a rheumatic-like preliminary phase. DIAGNOSES: The case reports of two patients with BCP ALL with a prodromal phase lasting a few weeks are presented. INTERVENTIONS AND OUTCOMES: DNA whole genome profile methylation analysis of bone marrow cells obtained at diagnosis revealed a pattern of methylation that was readily distinguishable from both healthy and standard course BCP ALL bone marrow samples. LESSONS: The biological implication of this observation remains unclear, with many differentially methylated loci involved in many processes like neurogenesis, cell projection organization and adhesion along with leucocyte activation and apoptosis. The prevalence and clinical significance of these methylation changes is unknown but this data indicates that the epigenetic basis of BCP ALL with a prolonged, prodromal phase requires a more detailed assessment.
Subject(s)
Bone Marrow Cells/metabolism , DNA Methylation , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prodromal Symptoms , Acute Disease , Child , Humans , MaleABSTRACT
In addition to genetic alterations, epigenetic abnormalities have been shown to underlie the pathogenesis of acute lymphoblastic leukemia (ALL)-the most common pediatric cancer. The purpose of this study was to characterize the whole genome DNA methylation profile in children with precursor B-cell ALL (BCP ALL) and to compare this profile with methylation observed in normal bone marrow samples. Additional efforts were made to correlate the observed methylation patterns with selected clinical features. We assessed DNA methylation from bone marrow samples obtained from 38 children with BCP ALL at the time of diagnosis along with 4 samples of normal bone marrow cells as controls using Infinium MethylationEPIC BeadChip Array. Patients were diagnosed and stratified into prognosis groups according to the BFM ALL IC 2009 protocol. The analysis of differentially methylated sites across the genome as well as promoter methylation profiles allowed clear separation of the leukemic and control samples into two clusters. 86.6% of the promoter-associated differentially methylated sites were hypermethylated in BCP ALL. Seven sites were found to correlate with the BFM ALL IC 2009 high risk group. Amongst these, one was located within the gene body of the MBP gene and another was within the promoter region- PSMF1 gene. Differentially methylated sites that were significantly related with subsets of patients with ETV6-RUNX1 fusion and hyperdiploidy. The analyzed translocations and change of genes' sequence context does not affect methylation and methylation seems not to be a mechanism for the regulation of expression of the resulting fusion genes.
