Reply to MacLeod et al.: Multiple myeloma plasma cells have chameleon characteristics

Breitkopf, Susanne B.; Yuan, Min; Pihán, Germán; Asara, John M.

doi:10.1073/pnas.1220582110

Cited by 2 publications

(2 citation statements)

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“…(Note that cell line NCI-H929 is listed in Version 8.0 of ICLAC’s Database of Cross-Contaminated or Misidentified Cell Lines ( http://iclac.org/databases/cross-contaminations ). However, its suspected misidentification 63 as a MM cell line by contamination with chronic myeloid leukemia (CML) cell line K562 was challenged 64 . We show in Supplementary Figs.…”

Section: Methodsmentioning

confidence: 99%

Harnessing a catalytic lysine residue for the one-step preparation of homogeneous antibody-drug conjugates

et al. 2017

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Current strategies to produce homogeneous antibody-drug conjugates (ADCs) rely on mutations or inefficient conjugation chemistries. Here we present a strategy to produce site-specific ADCs using a highly reactive natural buried lysine embedded in a dual variable domain (DVD) format. This approach is mutation free and drug conjugation proceeds rapidly at neutral pH in a single step without removing any charges. The conjugation chemistry is highly robust, enabling the use of crude DVD for ADC preparation. In addition, this strategy affords the ability to precisely monitor the efficiency of drug conjugation with a catalytic assay. ADCs targeting HER2 were prepared and demonstrated to be highly potent and specific in vitro and in vivo. Furthermore, the modular DVD platform was used to prepare potent and specific ADCs targeting CD138 and CD79B, two clinically established targets overexpressed in multiple myeloma and non-Hodgkin lymphoma, respectively.

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Section: Methodsmentioning

confidence: 99%

Harnessing a catalytic lysine residue for the one-step preparation of homogeneous antibody-drug conjugates

et al. 2017

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“…On the basis of FISH and reverse transcription (RT)-PCR analysis, MacLeod et al 62 have reported the H929 cell line on the International Cell Line Authentication Committee (ICLAC) list due to a suspected cross-contamination with K562 cell line in a study by Brietkopf et al 63 However, Brietkopf et al, in a subsequent and more detailed study 64 , have shown that their lot of H929 cell line was clearly of plasma cell origin and lacked most of the standard markers for the K562 cell line. Nevertheless, we obtained our MMCLs including the H929 from Dr Kuehl (NIH) and Dr Bergsagel (Mayo Clinic) and hence our study is not affected by the MacLeod's report.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional repression by the HDAC4–RelB–p52 complex regulates multiple myeloma survival and growth

et al. 2015

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Although transcriptional activation by NF-kB is well appreciated, physiological importance of transcriptional repression by NF-kB in cancer has remained elusive. Here we show that an HDAC4-RelB-p52 complex maintains repressive chromatin around proapoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth. Disruption of RelB-HDAC4 complex by a HDAC4-mimetic polypeptide blocks MM growth. RelB-p52 also represses BMF translation by regulating miR-221 expression. While the NIK-dependent activation of RelB-p52 in MM has been reported, we show that regardless of the activation status of NIK and the oncogenic events that cause plasma cell malignancy, several genetically diverse MM cells including Bortezomib-resistant MM cells are addicted to RelB-p52 for survival. Importantly, RelB is constitutively phosphorylated in MM and ERK1 is a RelB kinase. Phospho-RelB remains largely nuclear and is essential for Bim repression. Thus, ERK1-dependent regulation of nuclear RelB is critical for MM survival and explains the NIK-independent role of RelB in MM.

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Reply to MacLeod et al.: Multiple myeloma plasma cells have chameleon characteristics

Cited by 2 publications

References 4 publications

Harnessing a catalytic lysine residue for the one-step preparation of homogeneous antibody-drug conjugates

Harnessing a catalytic lysine residue for the one-step preparation of homogeneous antibody-drug conjugates

Transcriptional repression by the HDAC4–RelB–p52 complex regulates multiple myeloma survival and growth

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