Table 1 Summary of mutations and SNVs in CRBN and DDB1 in MM cell lines and patients

From: Absence of mutations in cereblon (CRBN) and DNA damage-binding protein 1 (DDB1) genes and significance for IMiD therapy

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

 
  1. 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.