General Information

• Official Cell Line Name: KMS-11

• Cell Line Series: KMS11

• Public Availability: JCRB Repository

• Keats Lab Name(s): KMS11_JPN , KMS11_JCRBadh, KMS11_JCRBsus

• Canonical Translocation(s): t(4;14), t(14;16), complex t(4;8;14) derived from duplicated der(14)t(4;14) allele

• Establishment Date: 

• Description of Establishment: 

Origin of KMS11 Series in the Keats Lab

We maintain three independent KMS-11 sub lines. 

The first version KMS_JPN we original provided to Dr. Keats by Takemi Otsuki while he was a graduate student with Linda Pilarski at the Cross Cancer Institute/University of Alberta. Upon arrival the cell line was largely adherent unlike other human myeloma cell lines, communication with Dr Otsuki highlighted the unique nature of KMS-11 being an adherent myeloma cell line with a small population of suspension cells. This cell line was subsequently maintained on tissue culture treated plastic and cells are passaged after an initial PBS wash to remove floating cells and trypsin inhibitors followed by trypsinization to release the cells for passage. This cell line has worked well for siRNA based studies.

The second and third versions of this cell line, KMS11_JCRBadh and KMS11_JCRBsus, were derived from a vial of KMS-11 cells purchased from the JCRB repository by Dr. Keats. Upon initiating culture we noticed there were two populations and adherent and suspension population. Given our background knowledge of the typical adherent nature of KMS-11 but the clear populations of suspension cells we attempted and were successful in establishing dedicated adherent and suspension cell lines. In these cases the adherent cell line, KMS11_JCRBadh, grows very similar to our KMS11_JPN version and the suspension line, KMS11_JCRBsus, is grows nearly universally as a suspension line like most all myeloma cell lines.

Our Sample Information

• Initial Culture Media: 

• Final Culture Media: AdvRPMI-1640 + 4% FBS

• Culture Additives: None

• Doubling Time: 

Translocation Breakpoint Details

KMS-11 is a unique cell line with three different immunoglobulin heavy chain translocations: t(4;14), t(14;16) and t(8;14) - MYC.  This is very atypical and even exceeds the number of IgH loci in a normal cell.  Furthermore, in all our work sequencing myeloma cell lines we have often struggled until we started using long-read technologies to properly define the der(14)t(4;14) breakpoint and the t(8;14) breakpoint.

Some details will still need to be resolved but this is our current understanding of the structures:

der(4)t(4;14) - This is a classic breakpoint in switch mu with a breakpoint in intron 1 of LETM1 on chromosome 14 bringing the Emu enhancer in proximity with NSD2

• <---JH6---Emu---Switch mu--//--LETM1 intron 1----NSD2--->

der(14)t(4;14) - This is an atypical breakpoint with a local duplication and inversion of the duplicated sequence on chr4 at the breakpoint.  The IgH breakpoint is also in switch mu

• <---FGFR3----LETM1---------//---------microduplication Inversion LETM1 Intron1----------//---IgH Switch mu---->

Complex der(14)t(4;8;14) derived from a suspect insertion of 8q24 into the inverted sequence on der(14)t(4;14) that occurs after the duplicaton of a der(14)t(4;14) allele

• <---FGFR3----LETM1------//-----SNTB1-------MYC--PVT1--LINC00824--//----microduplication Inversion LETM1 Intron1----------//---IgH Switch mu---->

der(14)t(14;16)

• <-----3' IgH E------------IgG1---Switch gamma1--//--WWOX----------MAF------>

der(16)t(14;16)

• <------WWOX--//----IGHV3-11---->

Questions to resolve:

1) are the t(4;14) and t(14;16) on different IgH haplotypes

2) Does a functional VDJ allele exist in these cells that is linked to a constant region

3) Are the two breakpoints between chr4 and chr8 an insertion of the 8q24 locus with MYC into the duplicated der(14)t(4;14)

• Can we assemble across this entire region?

• The identified t(4;8) is much lower in read counts and only seen in the long-read data so it could be a false positive.

  • If false there should be a copy number difference as FGFR3 would not be at 3x copies