Study of Thiopurine Methyltransferase gene polymorphism and rare genetic mutations to develop a treatment algorithm for reducing chemotherapy complications in children with acute lymphoblastic leukemia in Uzbekistan

Project Goal: Development of personalized treatment approaches for children with acute lymphoblastic leukemia (ALL) based on molecular-genetic data to reduce toxicity and improve therapy efficiency.

Key Objectives:

- Analysis of the TPMT gene mutation spectrum using DNA sequencing.

- Diagnostic evaluation of TPMT mutation carriers and polymorphisms for early detection (2025).

- Correlation study between mutations, 6-MP metabolite levels, and therapy toxicity and efficiency.

- Creation of a TPMT mutation and rare genetic variants database, including:

Karyotyping (hyper-/hypoploidy),
FISH (deletions/translocations: ABL1, PDGFRB, TP53, etc.),
PCR (JAK2, CALR, MPL, etc.) – (by 2026).

- Development of a treatment algorithm to reduce complications of chemotherapy in children with ALL based on the obtained data (by 2027).

Expected Outcomes:

- Improved diagnostic accuracy and therapy personalization.

- Reduced side effects and enhanced treatment prognosis.

- Implementation of molecular diagnostics in Uzbekistan’s clinical practice.

Project Leader: Doctor of Medical Sciences (DSc) S.Z. Ibragimova.