KMS-12-PE

Characterizations of KMS-12-PE Cell Lines

Most of the KMS-12-PE cells were small in size and round in shape with a few large distorted cells. Peroxidase, ASD-acetate esterase, and PAS staining were negative, and only the methyl-green-pyronine stain was positive in the cell lines. Ultrastructural, the cell lines revealed characteristic features of plasmacytoid cells, such as well-developed rough endoplasmic reticulum and ovoid eccentric nuclei with peripheral chromatin distribution (Fig. 1).

KMS-12-PE cells were positive for PCA-I, CD38, and OKT-9 (anti-transferrin receptor antibody). Representative karyotypes of KMS-12-PE and KMS-12-BM cells are shown in Fig. 2. Most of the metaphases of KMS-12-PE cells were hypodiploid, with the modal chromosome number being 41. In addition, all the metaphases of KMS-12-PE cells demonstrated a reciprocal chromosome translocation, t (9: 11) (q34; q13).

Fig. 1 Electron micrographs of KMS-12-PE cells. (Ohtsuki T, et al., 1989)

Fig. 2 Representative G-banded karyotypes of KMS-12-PE cells. (Ohtsuki T, et al., 1989)

Chromothripsis in Treatment Resistance in Multiple Myeloma

Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis of several cancers.

The frequency of copy number alterations (CNAs) was analyzed, including mosaicism in 9 MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929). Among them, chrs 1, 4, 5, 7, 8, and X were the sites with the most frequent CNAs in the MM cell lines (Fig. 3A). The chromosomes were divided into arms to confirm the trend of CNAs. According to the algorithm, if the copy number was 2.5 or more, it was considered an amplification, and if the copy number was 1.5 or less, it was considered a loss. Analysis of the tendency of CNAs showed that more CNAs were observed in the q arm than in the p arm (Fig. 3B and 3C).

Changes in CNAs were further analyzed in these cell lines by comparing CNAs after bortezomib (BTZ) treatment. Although the cell lines were derived from the same origin, the drug response between the two cell lines was different. In the case of KMS-12-BM, there was no difference in cell viability in the treatment group compared to the control, but in the case of KMS-12-PE, there was a sharp decrease in viability in the treatment group (Fig. 4).

Fig. 3 Analysis of the frequency of copy number alterations in MM cell lines. (Lee KJ, et al., 2017)

Fig. 4 Comparison of cell viability changes of KMS-12-BM and KMS-12-PE following treatment of bortezomib (BTZ). (Lee KJ, et al., 2017)