Table 2.
Characteristics of genes, their mutations, and pathological and treatment effects responsible for steroid, MTX, and asparaginase resistance.
| Gene and Locus | Gene’s Mutation | Effects on Pathology | Effects on Treatment |
|---|---|---|---|
| NR3C1 (locus 5q31.3) | Point mutations | Disordered transmission of signals via the NR3C1 receptor | Resistance to prednisone and dexamethasone |
| CREBBP (locus 16p13.3) | Sequence, deletion, missense mutations | amino acid substitutions in the histone acetyltransferase (HAT) domain | Resistance to steroids |
| DHFR (locus 5q14.1) | Single amino acid changes in DHFR, increased DHFR overexpression, decreased affinity of MTX for DHFR | Changes in metabolism of MTX | Resistance to MTX |
| TYMS (locus 18p11.32) | High expression of TYMS | Enhances purine production, cell proliferation | Resistance to MTX |
| FPGS (locus 9q34.11) | Low expression of FPGS | Plays role in MTX long-chain creation | Resistance to MTX |
| RFC1 (locus 4p14) | Less expression of RFC | insensitivity to apoptosis mechanisms | Resistance to MTX |
| ASNS (locus 7q21.3) | High expression of ASNS | Excessive synthesis of asparagine | Resistance to asparaginase |