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
2
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
2
