Characterization and use of the novel human multiple myeloma cell line MC-B11/14 to study biological consequences of CRISPR-mediated loss of immunoglobulin A heavy chain

Denise K. Walters, Bonnie K. Arendt, Renee C. Tschumper, Xiaosheng Wu, Diane F Jelinek

Research output: Contribution to journalArticle

Abstract

The genetic abnormalities underlying multiple myeloma (MM) are notoriously complex and intraclonal heterogeneity is a common disease feature. In the current study, we describe the establishment of a monoclonal immunoglobulin A (IgA) kappa (κ) MM cell line designated MC-B11/14. Cytogenetic and fluorescence in situ hybridization analyses of the original and relapse patient samples revealed that the MM clone was nonhyperdiploid and possessed an 11;14 chromosomal translocation. The MC-B11/14 cell line, established from the relapse sample, is tetraploid and houses the t(11;14) abnormality. Given our long-standing interest in Ig function and secretion, we next used CRISPR technology to knock out IgA heavy-chain expression in the MC-B11/14 cells to assess the biological consequences of converting this cell line to one only expressing κ light chains. As expected, secretion of intact IgA was undetectable from MC-B11/14IgA− cells. Sensitivity to pomalidomide treatment was similar between the MC-B11/14WT and MC-B11/14IgA− cells; however, MC-B11/14IgA− cells were found to be significantly more resistant to bortezomib treatment. This study describes the establishment of a new human MM cell line tool with which to study disease biology and the use of CRISPR technology to create a potentially useful model with which to study MM light-chain escape.

Original languageEnglish (US)
Pages (from-to)42-49.e1
JournalExperimental Hematology
Volume57
DOIs
StatePublished - Jan 1 2018

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Clustered Regularly Interspaced Short Palindromic Repeats
Immunoglobulin Heavy Chains
Multiple Myeloma
Immunoglobulin A
Cell Line
Technology
Light
Recurrence
Genetic Translocation
Tetraploidy
Fluorescence In Situ Hybridization
Cytogenetics
Clone Cells
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

Characterization and use of the novel human multiple myeloma cell line MC-B11/14 to study biological consequences of CRISPR-mediated loss of immunoglobulin A heavy chain. / Walters, Denise K.; Arendt, Bonnie K.; Tschumper, Renee C.; Wu, Xiaosheng; Jelinek, Diane F.

In: Experimental Hematology, Vol. 57, 01.01.2018, p. 42-49.e1.

Research output: Contribution to journalArticle

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