Table 1. Summary of mutations and SNVs in CRBN and DDB1 in MM cell lines and patients.
| IMiD-sensitive MM cell lines | CRBN nucleotide position and change | CRBN amino-acid position and change | DDB1 nucleotide position and change | DDB1 amino-acid position and change |
|---|---|---|---|---|
| H929 parental, U266, EJM, SKMM2 | None | None | ||
| OPM-2 | G1209A silent heterozygous | T403T | None | |
| KMS-12-BM parental | T735C silent homozygous | Y245Y | None | |
| Intrinsic IMiD-resistant MM cell lines | ||||
| LP1 | None | None | ||
| RPMI 8226 | None | None | ||
| JJN3 | None | None | ||
| Paired sensitive and acquired resistant cell lines | ||||
| H929 sensitive control | None | None | ||
| H929 4 resistant clones | None | None | ||
| KMS-12-BM sensitive control | T735C silent homozygous | Y245Y | None | |
| KMS-12-BM LEN-resistant | T735C silent homozygous | Y245Y | None | |
| KMS-12-BM POM-resistant | T735C silent homozygous | Y245Y | None | |
| MM1S sensitive | None | None | ||
| MM1S/R10R LEN-resistant | None | None | ||
| ANBL-6 sensitive | None | A909T heterozygous | E303D | |
| None | C153T silent heterozygous | P51P (rs2230356) | ||
| ANBL-6 LEN-resistant | G745T heterozygous | D249Y | A909T heterozygous | E303D |
| None | C153T silent heterozygous | P51P (rs2230356) | ||
| Patient samples (90) | ||||
| Newly diagnosed (24) | T735C silent homozygous, C219T silent heterozygous | 2 × Y245Y (rs17027638), 1 × H73H | C153T silent heterozygous, C939T silent heterozygous | 2 × P51P (rs2230356), 1 × C313C (rs150106100) |
| RRMM (30) | T735C silent homozygous | 2 × Y245Y (rs17027638) | C153T silent heterozygous | 4 × P51P (rs2230356) |
| LEN-resistant RRMM (36) | None | None | ||
Abbreviations: CRBN, cereblon; DDB1, DNA damage-binding protein 1; IMiD, immunomodulatory drug; LEN, lenalidomide; MM, multiple myeloma; POM, pomalidomide; RRMM, relapsed/refractory multiple myeloma; SNV, single-nucleotide variation.