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Samenvatting AML en MPN

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Samenvatting van de eerste 10 weken van de minor: Hemato-oncologie (MIN18xx). De onderwerpen Acute myeloïde leukemie en myeloproliferatieve neoplasma worden hier besproken.

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  • 5 november 2017
  • 17
  • 2017/2018
  • Samenvatting
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Summary MIN18xx Hemato-oncology


Index
Acute Myeloid Leukemia...................................................................................................................2
Clinical presentation:.........................................................................................................................2
Prognosis:..........................................................................................................................................7
Future:...............................................................................................................................................7
Flow cytometry.................................................................................................................................9
Markers..............................................................................................................................................9
Myeloproliferative neoplasms.........................................................................................................10
Chronic Myeloid Leukemia...............................................................................................................10
Chronic phase:.................................................................................................................................10
Clinical presentation:...................................................................................................................10
Diagnosis:.....................................................................................................................................10
Accelerated phase:...........................................................................................................................10
Blast phase:......................................................................................................................................10
Treatment: achieve major molecular response BCR-Abl/control gene ratio <0.1%..........................10
BCR-Abl/control gene ratio:.............................................................................................................11
Driver mutations..............................................................................................................................11
JAK2 Mutation..............................................................................................................................11
CALR Mutation.............................................................................................................................11
MPL Mutation..............................................................................................................................11
Additional acquired mutations.....................................................................................................11
Primary myelofibrosis......................................................................................................................12
Clinical presentation:...................................................................................................................12
Prognosis:.....................................................................................................................................12
Treatment:...................................................................................................................................12
Polycythemia Vera...........................................................................................................................12
Clinical presentation:...................................................................................................................12
Diagnostics:..................................................................................................................................13
Treatment:...................................................................................................................................13
Essential thrombocytosis..................................................................................................................13
Clinical presentation:...................................................................................................................13
Prognosis: IPSET score..................................................................................................................13
Treatment:...................................................................................................................................13
Appendix.........................................................................................................................................15
WHO Criteria CML (accelerated phase)............................................................................................15
WHO Criteria PV...............................................................................................................................15
WHO Criteria ET...............................................................................................................................15
WHO Criteria prePMF......................................................................................................................17
WHO Criteria overt PMF..................................................................................................................17

, Acute Myeloid Leukemia
Normal situation: only mature cells can be found in the peripheral blood following normal hematopoiesis  7
million blood cells per second.
Hematopoietic stem cell CD34+/CD38-
Lymphoid progenitor Myeloid progenitor

T cell B cell NK cells Granulocytes

AML: accumulation of immature myeloblasts in the bone marrow  takes a lot of space  suppressing normal
hematopoiesis. GF-independent proliferation, disturbed apoptosis and inhibited differentiation.
Type I mutation: problem in signal transduction  affecting proliferation
Type II mutation: problem in transcription factors  affecting differentiation.
AML = type I + type II mutations.

Causes:
 Bad luck most of the time: accumulation of somatic mutations during aging
 Hereditary diseases: Down syndrome, falconi anemia
 Chemicals
 Toxic drugs (chemotherapy)
 Radiation

Clinical presentation:
 Non-specific (general) symptoms: fatigue, fever, night sweats, loss of apetite, malaise.
 Anemia, leukopenia, neutropenia, thrombocytopenia
 Bleeding (hemorrhages, nose bleeds, menorrhagiableeding that won’t stop)
 Gout (rare)
 Recurrent infections
 EMD (myeloblasts in other organs)
 Leukostasis (high viscosity of the blood caused by the high number of leukocytes)
 Swelling of spleen and liver
 Skin abnormalities (petechia, hematoma, chloroma, erythema nodosum)

Diagnostics: bone marrow and peripheral blood
 Blood count
 Blood smear: visible blasts, lymphoid or myeloid?
 Bone marrow aspiration and biopsy
 Morphology (FAB)  classification M0 – M7
o M0: Undifferentiated acute myeloblastic leukemia
o M1: AML with minimal maturation
o M2: AML with maturation
o M3: Acute promyelocytic leukemia  different treatment  arsenic + vitamin A (proven to be
effective)
o M4: Acute myelomonocytic leukemia
o M5: Acute monocytic leukemia
o M6: Acute erythroid leukemia
o M7: Acute megakaryocytic leukemia
o Other classifications: chemotherapy + stem cell transplantation (either autologous or
allogeneic)
 Cytochemistry: chemical stains (dyes) only react with a certrain type of cells and then can be visualized
under the microscope.
 Cytogenetics: search for structural/numeric abnormalities in the chromosomes via karyotyping or FISH.
 Molecular diagnostics: search for translocations and mutations. Contributes to diagnosis, prognosis,
risk stratification, treatment decisions and precision medicine.
o Chromosomal aberrations e.g. translocations (+- 50% of AML): FISH, SNP array, cytogenetics


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