Lec 16 Flashcards
what are myeloid cells
granulocytes
monocytes
erythrocytes also
and megakaryocytic cell lineages
the 2 types of myeloid leukemia u need to know
- acute myeloid leuk
- chronic myeloid leuk
official WHO classification system
20% blast cell count in either blood, or bvone marrow
chromosome translocations
dysplasia
which group is aml most common in
65+ yrs old
what are the 2 most ccommon AML genetic mutations
- transloc between chrom 8 and 21 [t(8;21)]
- transloc between chrom 15 and 17
what might be an exception to the WHO diagnosis
if you see the particular genetic abnormality (e.g. PML-RARA) you dont need the 20% blast count to diagnose
whats a non cytogenetic testing way to possibly identify a malignant cell under the microscope
Auer rods
an accumulation of a certain protein
this was useful pre cytogenetic tests
how does FAB classification work
based on morphology, visualising what stage the cell is at
goes from M0 to M7 (and has subcategories)
what is FAB class M3
acute promyelocytic leukemia (APML)
which translocation is M3 APML
15 to 17
APML: which gene is on chrom 15
promyelocytic leukaemia gene (PML)
APML: what gene is on chrom 17
retinoic acid receptor alpha gene (the gene from 15 fuses with this one to form fusion product)
APML: what does the fusion product do
blocks differentiation of the cells
what can M3 APML be treated with
all-transretinoic acid (ATRA)
degrades the fusion product
which induces differentiation
what is M2 AML
granulated blasts with Auer rods
what translocation is the M2 AML
8 and 21
M2: what gene is on chrom 21 adn what does it do
AML1
- codes for alpha chain of a transcriptional apparatus called CORE BINDING FACTOR (CBF)
- critical for haemotpoietic development
M2: what gene is on chrom 8
ETO gene
M2: what happens when the translocation happens (effect of fusion gene)
Causes RUNX1 and RUNx1T1 to come together
which blocks transcription of genes needed for myeloid differeniation
what type of thingy is RUNx1T1
a co repressor
M2: what type of blasts usually seen in this disease
promeylocytes and myelocytes
clinical features ofAML
- anamia
- thrombocytopenia
- infections
- skin inflitration
- CNS disease
process of diagnosing AML
- full blood count
- blood film
- bone marrow smear
- immunophenotyping
- cytogenetics
what are some supportive treatments of AML
Treatment of bone marrow failure
Episodes of fever
what is chemotherapy divided into
induction (remission-reduction) and
consolidation (post induction) phases.
what is aim of induction therapy
achieve a complete remission (<5% blasts in bone marrow, normal blood counts, clinical status)
what is aim of consolidation
to eliminate any residual cells
the main 2 types of induction chemotherapy drugs
- cytarabine
- antracycline
what is M3 subtype treated
ATRA
combined with standard chemo
what is consoldiation therapy based on
prognostic factors
changes the amount of lenght of consolodiation therapy
what is CD33
a molecule expressed by meyeloid stem cells that can be used as a identifying marker
name the Anti CD33 drug
mylotarg
now is used alongside the chemotherapy drugs mentioned before
what is myelotoxicity side effect of cytotoxic drugs
limited selectivity between leukemic and normal marrow cells
can even lead to bone marrow failure
2 types of stem cell transplantation
autologous
allogenic
what is autologous stem cell transplant
- patient’s own marrow
- taken when theyre in remission
what is allogenic transplantation
marrow from normal donor (usually someone related, with same tissue type)
how does age affect prognosis
- 50% of young adults and kids cna be cured
- but less than 5% of over 65
