PSH_CML

This disease is driven by BCR/ABL1 chimeric gene known as the Philadelphia chromosome

• AML

• ALL

• CML

• CLL

Answer explanation

CML - driven by BCR/ABL1 coding long arms of chromosome 9 and 22 or t(9,22)(q34.1lq11.2) known as Philadelphia Chromosome

Which of the following gene mutation is assocated with worse response to therapy and higher risk of transformation to blastic phase in CML, EXCEPT?

• IKZF1

• RUNX1

• ASXL1

• CSF3R

Answer explanation

CSF3R mutation may respond well to ruxolitinib (a JAK2 inhibitor) therapy with complete response in 50-60% of patients.

The following mutation in CML responds better with Nilotinib except?

• V299L

• T315A

• F317/F/I/C

• F359V/C/I

Answer explanation

Responds best to Dasatinib and Bosutinib:

Y253H, E255K/V and F359V/C/I

Which of the following is a 3rd generation TKI?

• Bosutinib

• Nilotinib

• Dasatinib

• Ponatinib

Which of the following TKI is has no approved indciation on blastic phase?

• Bosutinib

• Nilotinib

• Dasatinib

• Ponatinib

Answer explanation

Indications:

Bosutinib - all phases

Dasatinib - all phases

Ponatinib - all phases

Nilotinib - all phases except blastic phase

Which of the following TKI has the lowest incidence of cardiovascular events?

• Bosutinib

• Nilotinib

• Imatinib

• Ponatinib

Answer explanation

The bos! - lowest incidence of CVD event

- inhibits SRC family of kinases in addtion to ABL1

• - no activity against c-kit or PDGFR

Which of the following BCR-ABL1 TKI has significant efficacy against T3151?

• Imatinib

• Dasatinib

• Nilotinib

• Ponatinib

Answer explanation

Ponatinib

• -inhibits VEGFR

• - only BCR/ABL1 TKI active against T315I (a gatekeeper mutation resistant to other ATP competitive TKI)

• - approved on all phases

• Side Effects: skin rashes, pancreatitis, arterio occlusive disease and Systemic Hypertension

Approved for treatment for chronic and accelerated phase after failure of 2 or more TKI

• asciminib

• olverembatinib

• omacetaxine mepesuccinate

• Ponatinib

Brand name of Imatinib

Brand name of Bosutinib