CD34+ myeloma cells with self-renewal activities are therapy-resistant and persist as MRD in cell cycle quiescence.

Autor: Serizawa, Kentaro, Tanaka, Hirokazu, Ueda, Takeshi, Fukui, Ayano, Kakutani, Hiroaki, Taniguchi, Takahide, Inoue, Hiroaki, Kumode, Takahiro, Taniguchi, Yasuhiro, Rai, Shinya, Hirase, Chikara, Morita, Yasuyoshi, Espinoza, J. Luis, Tatsumi, Yoichi, Ashida, Takashi, Matsumura, Itaru
Zdroj: International Journal of Hematology; Mar2022, Vol. 115 Issue 3, p336-349, 14p
Abstrakt: Side population (SP) is known to include therapy-resistant cells in various cancers. Here, we analyzed SP using multiple myeloma (MM) samples. The SP accounted for 2.96% in MM cells from newly diagnosed MM (NDMM). CD34 was expressed in 47.8% of SP cells, but only in 2.11% of bulk MM cells. CD34+ MM cells expressed more immature cell surface markers and a gene signature than CD34- MM cells. CD34+ but not CD34- MM cells possessed clonogenic activities and showed long-term self-renewal activities in xenotransplantation assays. Similarly, whereas 2.20% of MM cells were CD34+ in NDMM (n = 38), this proportion increased to 42.6% in minimal residual disease (MRD) samples (n = 16) (p < 0.001) and to 17.7% in refractory/relapsed MM (RRMM) (n = 30) (p < 0.01). Cell cycle analysis showed that 24.7% of CD34+ MM cells from NDMM were in G0 phase while this proportion was 54.9% in MRD (p < 0.05) and 14.5% in RRMM, reflecting the expansion of MM. Together, CD34+ MM cells with long-term self-renewal activities persist as MRD in cell cycle quiescence or remain as therapy-resistant cells in RRMM, substantiating the necessity of targeting this population to improve clinical outcomes of MM. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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