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1. The physiological oxygen level within the bone marrow of AML patients is approximately 6%, and hypoxic stress at this level increases surface expression of the CXCR4 receptor on AML cells. 2. Hypoxic AML cells exposed to 6% oxygen show increased migration towards the stromal cell-derived factor SDF-1 compared to cells exposed to 21% oxygen. 3. CXCR4 expression and downstream signaling are constitutively upregulated under physiological 6% oxygen levels through a non-transcriptional mechanism involving lipid rafts.
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Cell cycle regulation
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https://www.creative-bioarray.com/cell-cycle-assays.htm
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Cell cycle refers to the set of events through which a cell grows, replicates its genome, and ultimately divides into two daughter cells through the process of mitosis.
https://www.creative-bioarray.com/cell-cycle-assays.htm
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Each human cell contains 23 pairs of chromosomes. Most cases of CML start when a "swapping"
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This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
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Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
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Presentation4
- 1. Acute Myeloid Leukemia CXCR4 Oxygen partial pressure 1
- 3. Chemokine and its receptor Receptor Receptor = CXCR4 Chemokine Chemokine = SDF1 3
- 4. CXCR4/SDF-1 Stromal cell SDF-1 CXCR4 4
- 5. In vitro vs In vivo? Physiological Oxygen level 5 O2 level within bone marrow is ~6.8%.
- 6. “CXCR4 expression and biologic activity in acute myeloid leukemia are dependent on oxygen partial pressure” - Michael Fiegi et al; Blood ; 2009 6
- 7. 1.What is the Oxygen level in bone marrow of AML patients? 19 AML patients 6.06% (+1.7%) <10 min Physiological level of O2 within bone marrow of AML patients is 6%. 7
- 8. 2. Does Oxygen level influence CXCR4 expression in AML? AML cell AML cell ? Hypoxic stress CXCR4 8
- 9. Surface expression of CXCR4 increases at 6% 02 AML cell AML cell AML cell 6% O2 21% O2 Hypoxic stress CXCR4 9
- 10. 3. Does hypoxic AML cells migrate better to stromal factor (SDF-1)? 10
- 11. 3. Does hypoxic AML cells migrate better to stromal factor (SDF-1)? AML cell Hypoxic Stromal cell 11
- 12. 4.What are downstream signaling effects of CXCR4-SDF1? Downstream signals are constitutively upregulated under “physiological O2 level” of 6%. 12
- 13. 5.What are the kinetics of CXCR4 regulation? 21% 02 6% 02 AML AML Increased Transcription? CXCR4 m RNA 13
- 14. 5.What are the kinetics of CXCR4 regulation? 6% 02 21% 02 AML AML 5 min CXCR4 regulation to O2 levels is NOT regulated transcriptionaly. CXCR4 14
- 15. Lipid rafts as sites for regulation of protein expression 21% 02 21% 02 6% 02 AML AML AML 15
- 16. The experiment 6% 02 AML 6%->21 02 AML 21% 02 AML 16
- 17. 21% 02 6% 02 21% 02 AML AML AML Lipid rafts are regulators of chemokine expression. ? CXCR4 Lipid Raft 17
- 18. Shedding of CXCR4 as microparticles 6% 02 6% -> 21% 02 Protein Supernatant Cellular component Western Blot of Sup 18
- 19. Points to consider 19 21% ->6% -> 21% 6.8% -> 6% ->21%
- 20. Summary (1) “ Always perform your experiment at physiological Oxygen level so that you don’t miss out on the 3P’s.” 20 Protein Regulation Protein Shedding Publication in Blood
- 21. Summary (2) AML cell AML cell 6% Oxygen Stromal cell 21
- 22. 22 Subhashis Sarkar PhD student, Tumor Immunology