ITPA (Inosine Triphosphatase)

This case is the first to document direct PTC invasion of an ITPA and highlights the importance of surgical excision in suspected ITPA, both for definitive treatment and to uncover occult malignancy. This paper aims to present the first reported case of concurrent ITPA and PTC within the same lobe, with histologically confirmed direct carcinoma invasion into the adenoma, review the existing literature on this rare coexistence and highlight the associated diagnostic challenges and surgical considerations.

Excessive 6-thioguanine (6-TGN) levels worsen neutropenia, while elevated 6-methylmercaptopurine (6-MMP) levels contribute to hepatotoxicity. In contrast, two variants in the IMPDH1 gene, rs2228075 and rs2278294, are correlated with more frequent neutropenia. These findings highlight novel genetic variants influencing 6-MP metabolism and toxicity in paediatric ALL patients.

The integration of functional SPECT data with anatomical CT details allows for confident differentiation from thyroid nodules and alters surgical strategy, enabling targeted resection and minimizing the risk of failed exploration. We advocate for the expedited use of this hybrid imaging technique in the diagnostic workflow of PHPT when ectopic or intrathyroidal lesions are suspected, ensuring complete resection and biochemical cure while preserving normal parathyroid function.

The most studied genes were TPMT and CYP3A5, which are involved in the metabolism of 6-mercaptopurine (6-MP) and vincristine, respectively...Chemotherapies frequently studied were 6-MP (reported in five studies), vincristine, cyclophosphamide, and methotrexate...However, research remains regionally limited, and gaps in infrastructure and healthcare worker training persist. Expanding research efforts and improving pharmacogenomics capacity through pharmacist training and capacity-building initiatives are essential to advancing personalized medicine in Africa, ultimately improving treatment outcomes for pediatric cancer patients.

Sri Lankans exhibit higher frequencies in variants reducing methotrexate efficacy (SLC19A1), increasing azathioprine myelotoxicity (NUDT15), and lower frequencies in variants linked to increased azathioprine toxicity (TPMT*3B, TPMT*3C), reduced tacrolimus efficacy (CYP3A4*18), and methotrexate toxicity risk (MTHFR). Beneficial variants enhancing rituximab efficacy (FCGR3A) are more prevalent, while those reducing tacrolimus dosage (CYP3A5*6) are less common. This highlights need for targeted medication strategies to improve treatment outcomes.

This systematic review strongly supports the further investigation of DNA-TG as a marker for monitoring thiopurine therapy. Its correlation with treatment outcomes, such as relapse-free survival in ALL and the risk of leukopenia in IBD, underscores its role in enhancing personalized treatment approaches. DNA-TG effectively identifies NUDT15 variants and predicts late leukopenia in patients with IBD, regardless of their NUDT15 variant status. The recommended threshold for late leukopenia prediction in patients with IBD with DNA-TG is suggested to be between 320 and 340 fmol/µg DNA. More clinical research on DNA-TG implementation is mandatory to improve patient care and to improve inclusivity in thiopurine treatment.

Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.

We report no significant association between ITPA rs1127354 genetic polymorphism and adverse effects in the South Indian patients on AZA therapy.

In contrast, after multivariate analysis, relapse hazard ratio (HR) increased in ALL children of the intermediate risk arm compared to those in standard risk arm (3.44, 95% confidence interval (CI), 1.31-9.05, p= 0.012), and in carriers of the PACSIN2 rs2413739 T allele compared to those with the CC genotype (heterozygotes CT: HR, 2.32; 95% CI, 0.90-5.97; p=0.081; homozygous TT: HR, 4.14; 95% CI, 1.54-11.11; p=0.005). Future studies are needed to confirm the lack of impact of TGN levels and variability on relapse in the AIEOP-BFM ALL trials, and to clarify the mechanism of PACSIN2 rs2413739 on outcome.

In conclusion, in this cohort, XDH rs2281547 was identified as a genetic risk factor for grade 4 hematologic toxicities in ALL patients treated with 6-MP. Genetic polymorphisms in enzymes other than TPMT involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.

This is a rare presentation of a common endocrinopathy. These patients were noted to have PHTP. Initial exploratory neck dissections did not localize.