• Annals of Laboratory Medicine
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• 제38권6호
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• pp.495-502
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• 2018

Background: Molecular genetic abnormalities are observed in over 90% of chronic myelomonocytic leukemia (CMML) cases. Recently, several studies have demonstrated the negative prognostic impact of ASXL1 mutations in CMML patients. We evaluated the prognostic impact of ASXL1 mutations and compared five CMML prognostic models in Korean patients with CMML. Methods: We analyzed data from 36 of 57 patients diagnosed as having CMML from January 2000 to March 2016. ASXL1 mutation analysis was performed by direct sequencing, and the clinical and laboratory features of patients were compared according to ASXL1 mutation status. Results: ASXL1 mutations were detected in 18 patients (50%). There were no significant differences between the clinical and laboratory characteristics of ASXL1-mutated ($ASXL1^+$) CMML and ASXL1-nonmutated ($ASXL1^-$) CMML patients (all P >0.05). During the median follow-up of 14 months (range, 0-111 months), the overall survival (OS) of $ASXL1^+$ CMML patients was significantly inferior to that of $ASXL1^-$ CMML patients with a median survival of 11 months and 19 months, respectively (log-rank P =0.049). An evaluation of OS according to the prognostic models demonstrated inferior survival in patients with a higher risk category according to the Mayo molecular model (log-rank P =0.001); the other scoring systems did not demonstrate a significant association with survival. Conclusions: We demonstrated that ASXL1 mutations, occurring in half of the Korean CMML patients examined, were associated with inferior survival. ASXL1 mutation status needs to be determined for risk stratification in CMML.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.94-108
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• 2023

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.