CML Flashcards
Does CML happen in kids?
no
What kind of disorder is CML and what others are involved?
Myeloproliferative
- PV, ET and MF
what are some findings in CML?
Basophilia
WBC increased
Left shift of neuts
decreased LAP
What are the sx of CML?
Night sweats fevers Fatigue Slow onset Abdominal pain or fullness
What is the translocation in CML?
9 to 22 translocation
BCR-ABL fusion- continuous active tyrosine kinase
- Imantinub 1st line
What is a teardrop cell indicitive of?
Chronic myelofibrosis
- trying so hard to get out of crowded BM
CML arises from defects in what diff pathway?
Neurophil
Do BCR-ABL have ability to self renew?
No
- must have another mutation because of prolif
- GMP acquires ability to self renew and huge blast phase expansion
- this activatd WNt-B catenin
are BCR or ABL oncogenic alone?
no
- ABL is DNA repair and cytoskeleton repair
- BCR is inhibition of some inflame responses
What is lost and what is gained in the BCR-ABL?
BCR gains tyrosine 177 which is new binding site for proteins and coiled coil domain
- ABL looses myristate which is its inhibition factor
How does Imantinib work?
Blocks ATP binding sites and inactivated tyrosine kinases
- dont work against blast phase
What is so special about CML?
Rare example of single defect= disease
What is Imantinub metabolized by?
CYP3A4 which is the grapefruit one
-
What is Nilotinib?
Faster and deeper remission
What is Dasatinib and Bosutinib?
active against most point mutations of except T315I
- fluid retention and pulmonary HTN
- 30% of plp failing imantinib have this mutation
