Applied Microscopy

  • Volume 51
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  • Pages.20.1-20.12
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  • 2021
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  • 2287-5123(pISSN)
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  • 2287-4445(eISSN)
Korean Society of Microscopy (한국현미경학회)
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Ultrastructural changes in cristae of lymphoblasts in acute lymphoblastic leukemia parallel alterations in biogenesis markers

  • Ritika Singh (Department of Biochemistry, Teaching Block, All India Institute of Medical Sciences) ;
  • Ayushi Jain (Department of Biochemistry, Teaching Block, All India Institute of Medical Sciences) ;
  • Jayanth Kumar Palanichamy (Department of Biochemistry, Convergence Block, All India Institute of Medical Sciences) ;
  • T. C. Nag (Department of Anatomy, Teaching Block, All India Institute of Medical Sciences) ;
  • Sameer Bakhshi (Department of Medical Oncology, BRAIRCH, All India Institute of Medical Sciences) ;
  • Archna Singh (Department of Biochemistry, Teaching Block, All India Institute of Medical Sciences)
  • Received : 2021.09.29
  • Accepted : 2021.12.18
  • Published : 2021.12.31
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Abstract

We explored the link between mitochondrial biogenesis and mitochondrial morphology using transmission electron microscopy (TEM) in lymphoblasts of pediatric acute lymphoblastic leukemia (ALL) patients and compared these characteristics between tumors and control samples. Gene expression of mitochondrial biogenesis markers was analysed in 23 ALL patients and 18 controls and TEM for morphology analysis was done in 15 ALL patients and 9 healthy controls. The area occupied by mitochondria per cell and the cristae cross-sectional area was observed to be significantly higher in patients than in controls (p-value=0.0468 and p-value<0.0001, respectively). The mtDNA copy numbers, TFAM, POLG, and c-myc gene expression were significantly higher in ALL patients than controls (all p-values<0.01). Gene Expression of PGC-1α was higher in tumor samples. The analysis of the correlation between PGC-1α expression and morphology parameters i.e., both M/C ratio and cristae cross-sectional area revealed a positive trend (r=0.3, p=0.1). The increased area occupied by mitochondria and increased cristae area support the occurrence of cristae remodelling in ALL. These changes might reflect alterations in cristae dynamics to support the metabolic state of the cells by forming a more condensed network. Ultrastructural imaging can be useful for affirming changes occurring at a subcellular organellar level.

Keywords

Acknowledgement

We would like to acknowledge Dr. Shilpi Chaudhary, from BRAIRCH, for her help with data analysis and for providing primers for CS and c-myc. We would like to thank Mrs. Chanda, Mr. Sandeep and Mr. Girish from the EM facility, AIIMS for their help in TEM sample processing and obtaining images. The contribution from nurses and research staff is greatly appreciated for their facilitation of patient sample collection and access to data records. Finally, we gratefully acknowledge the support and cooperation of the patients and their care providers for agreeing to participate in the study.

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