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Printable Handouts
Navigable Slide Index
- Introduction
- Multiple myeloma (MM) - Overview
- Multiple myeloma (MM) - Symptoms
- Multiple myeloma (MM) - Diagnosis
- Treatment of MM
- Treatment of MM - Drug resistance (DR)
- Bone marrow (BM) microenvironment
- Exosomes - Overview
- Exosomes in cancer and as biomarkers
- Exosomes - Isolation procedures
- Exosomes - Ultracentrifugation
- Exosomes - Gradient centrifugation
- Exosomes - Size exclusion chromatography
- Exosomes - Immunomagnetic isolation
- Exosomes - Exoquick kit
- Exosomes - Confirmation
- BM - Angiogenesis, Osteolysis, Drug resistance
- Exosomes in MM - Angiogenesis
- Investigating MM biology - Models
- Characterisation of MM exosomes
- Exosome cargo
- Role of hypoxia
- Hypoxia resistant MM cells stimulate angiogenesis
- miR135b cargo in MM exosome vesicles (EVs)
- miR340/365 in BM EVs: angiogenesis suppression
- Exosomes in MM - Osteolysis
- MM exosomes are taken up by osteoclasts
- MM exosomes stimulate osteoclasts
- MM exosomes support osteoclast survival
- MM exosomes stimulate osteoclasts via IL32
- MM exosomes inhibit osteoblasts
- Exosomes in MM - questions about drug resistance
- BMSC exosomes are picked up by MM cells
- Migration & proliferation of MM cells
- BMSC exosomes induce survival of MM cells
- BMSC induce resistance to bortezomib
- Drug resistance - Exosome cargo
- Healthy BMSC exosomes inhibit MM growth
- Role for IL6 and fibronectin in MM growth
- Role for miR15a in BMSC EVs in MM suppression
- miR146a transfer from MM cells to BMSC
- miR146a mimics increase MM viability & migration
- MM exosomes induce BMSC to CAF transition
- Role for miR21/146a
- Exosomes in MM - Conclusion (recap)
- Drug exposure increases exosome secretion
- Chemoexosomes & more heparanase on surface
- Heparanase in MM cells & cell cycle regulation
- Exosomes in MM - biomarkers
- Take home message
- Acknowledgments
Topics Covered
- Introduction to the biology of Multiple Myeloma
- The development of drug resistance in Myeloma
- The role of the bone marrow environment in drug resistance
- The concept of exosomes
- Points of attention when dealing with exosomes
- The role of exosomes within the bone marrow environment
Links
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Talk Citation
Menu, E. (2018, December 30). The role of exosomes in multiple myeloma development & drug resistance [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 20, 2024, from https://doi.org/10.69645/VORJ4631.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Eline Menu has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms
Transcript
Please wait while the transcript is being prepared...
0:00
Hello my name is Eline Menu.
I am from the Hematology and Immunology lab of the Free University of Brussels.
Today, I will talk to you about the role of exosomes
and multiple myeloma developments and drug resistance.
0:14
Multiple myeloma is an incurable plasma cell malignancy.
It's the second most common hematological malignancy
with an incidence of six people in a 100,000.
The average age of diagnosis is 65 years with an average survival of three to four years.
0:30
Multiple myeloma develops in the bone marrow.
There, the myeloma blown will expand and this will lead to the secretion of
a monoclonal immunoglobulin or M-spire
the induction of osteolysis and the induction of angiogenesis.
This altogether, will lead to the typical what we call CRAB
symptoms which stand for hyperCalcemia Renal failure,
Anemia and Bone lesions.
Myeloma patients will also have vague symptoms including fatigue and infections.
1:01
The diagnosis of multiple myeloma most
often occurs by measuring the M spike in serum or urine.
As you can see on the right,
this is an electrophoresis profile,
and in the far right corner you have gamma proteins there.
You can now see a peak.
Normally in healthy patients,
this is a more of a plateau because there are different kinds of immunoglobulins.
But with a myeloma patient,
there's one million clone secreting one type of immunoglobulin which causes the peak.
So the diagnostic criteria are 10% plasma cells in the bone marrow
and M spike of more than three grams per deciliter and at least one of the crap symptoms.
Myeloma is often preceded by a premalignant stage
called Monoclonal Gammopathy of Undetermined Significance or MGUS.
These patients have a detectable M spike,
but they do not have one of the CRABs symptoms,
and they have less than 10% plasma cells on a bone marrow smear.
However these patients are more closely monitored because they
can proceed to myeloma more often than a healthy person.
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