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Samenvatting - BMS72 Cancer Development and Immune Defense (MED-BMS72)
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Cancer DevelopmentLE – Introduction – 28/10
Cancer development and immune defense
Hematological cancers are often already metastasized because they are not solid cancers
Cancer
immunoediting
,
, LE – Stem Cell Biology – 28/10
Promyelocytic leukemia with mutated oncogenic transcription factor
Cure rate 40% with intensive chemotherapy
State-of-the-art combination therapy
o Retinoic acid (vitamin A) and arsenic trioxide (rat poison)
o Both bind oncogenic transcription factors which leads to proteasomal degradation
o Differentiations of leukemia cells, apoptosis
The key to cure is understanding disease pathogenesis and cells that are involved
Normal hematopoiesis
Hematopoiesis occurs in the bone marrow
Hematopoietic stem cells (HSC)
Quiescent: not actively dividing and in a “rest” state
o 1 cell division every 25-50 weeks
Present during a full lifetime
Protected against mutations
Recognizing blood cell populations
Markers of HSCs
o CD34+
o CD38-
, o Thy-1+
o c-kit+
o IL-3R-
Characterizing hematopoietic cells with flow cytometry and
specific markers
However, we cannot identify stem cells just with cell surface
markers, because you only identify populations with this. Besides cell surface markers you can also
do functional assays (self-renewal assays and differentiation potential tests), look at molecular
characteristics (epigenetic marks) etc. Specific cell transplantations in mice are used for this, this way
the behavior can be tracked over time which provides insights into whether the cells function as
stem cells. Nucleated cells have a very short lifespan in comparison to stem cells.
Long term hematopoiesis (>9 months): demonstrates the ability to self-renew and
differentiate
Contribution to all blood lineages: shows that HSCs can become all cell lines in blood
Transplantation/ reconstitution with 1 cell: serves as evidence that one cell can lead to
generation of a complete and functional hematopoietic system
Development of leukemia
Leukemia= disbalance in proliferation/ differentiation/ apoptosis caused by genetic mutations
>20% immature cells in bone marrow
Morphological classification: immature M0 - M7 mature
Types:
o myeloid vs. lymphoid
o Acute vs. chronic
Classification of subtypes
o Early days: morphological classification
o Present days: include genetic classification
It is very hard to identify leukemia due to general symptoms in early leukemia. There are some
treatments aimed at cure when leukemia is diagnosed
2 courses of very intensive chemotherapy
AML subtype specific treatment regimes
Autologous transplantation/ allogeneic transplantation > dependent on subtype
Average cure rate:
o 40% below 60 yrs
o 10% above 60 yrs
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