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. 2014 May;28(5):1155-8.
doi: 10.1038/leu.2013.383. Epub 2013 Dec 24.

ALDH1 activity identifies tumor-initiating cells and links to chromosomal instability signatures in multiple myeloma

W Zhou  1 , Y Yang  1 , Z Gu  1 , H Wang  1 , J Xia  1 , X Wu  2 , X Zhan  3 , D Levasseur  1 , Y Zhou  1 , S Janz  4 , G Tricot  1 , J Shi  2 , F Zhan  1
Affiliations

ALDH1 activity identifies tumor-initiating cells and links to chromosomal instability signatures in multiple myeloma

W Zhou et al. Leukemia. 2014 May.
No abstract available

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Figures

Figure 1
Figure 1. A small set of ALDH1+ population induces clonogenic ability and tumor formation in myeloma cells
(A) Representative FACS analysis of the ALDH1+ population in HMCL, ARP1, showed the MM cells without DEAB treatment shifted to the right were considered as ALDH1+ cells (right panel) analyzed by the Aldefluor assay. (B) The percentage of ALDH1+ cells in HMCLs exhibits ~48.5-fold differences, ranging from ~0.1% in case of OPM2 to ~4.85% in case of KMS12BM. Mouse myeloma cells, 5TGM1, fall in the top range of human cell lines. (C) The FACS analysis of ALDH1+ and ALDH1+/ κ+ population shows an existence of low percentage double positive MM cells in primary sample. (D) ALDH+ cells (left) are more clonogenic than ALDH- cells (right). Shown are photographic images of ARP1 and KMS12BM cells forming colonies on soft agar. Colonies were enumerated using a light microscope and means and standard deviations of the mean are indicated at bottom right. The difference in mean colony number of ALDH+ and ALDH− cells was statistically significant (p < 0.05) using Student's t test. Morphologic pictures were taken under microscope and number of colonies of ALDH+ and ALDH− cells from ARP1 and KMS12BM cells (p < 0.05). Tumorigenicity was evaluated in a xenograft model, mice were injected with ALDH1+ and ALDH1− cells from ARP1 and KMS12BM cells, (E) and tumors dissected from (F) were shown.
Figure 2
Figure 2. Identification of ALDH1 related signatures
(A) A heat map showed 20 genes differentially expressed between ALDH1+ and ALDH1− MM cell lines. (B) A supervised cluster exhibited 20 ALDH1+ associated genes in plasma cells from 22 healthy subjects (NPC), 44 subjects with MGUS, 351 patients with newly diagnosed MM and 9 human MM cell lines (MMCL). Samples within myeloma AAS were ordered so that the predicted AASS increases continuously from left to right. (C) ~ (F) Kaplan-Meier analyses revealed MM patients with a high-AASS had inferior event-free and overall survivals in newly diagnosed TT2 and TT3 cohorts. (G) A scatter-plot showed a positive correlation between the 70-gene risk score (Y-axis) with the ALDH1-associated signature score (AASS) (X-axis). (H) A box-plot showed increases of AASS (Y-axis) in aggressive myeloma genetic subgroups (X-axis) of proliferation (PR) and MAF/MAFB (MF).
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References

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