CML

Question 1

Clonal hematopoietic myeloproliferative stem cell neoplasm

Driven by the BCR/ABL1 chimeric gene that codes for a constitutively active tyrosine kinase resulting from a reciprocal balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34.1;q11.2) - the Philadelphia chromosome (Ph)

Answer 1

CML

Question 2

Only proven risk of CML

Answer 2

IONIZING RADIATION

peak risk 5–10 years post-exposure

Question 3

Present in >90% of CML

produces BCR-ABL1 fusion gene

encodes constitutively active tyrosine kinase

Answer 3

t(9;22)(q34;q11) – Philadelphia chromosome

e13a2 / e14a2

Question 4

BCR ABL causes

Answer 4

↑ Proliferation
↑ Genetic instability
↓ Apoptosis
↓ Stromal adhesion

Question 5

CML stem cells difficult to cure due to

Answer 5

RESISTANT PATHWAYS:
β-catenin
Wnt
FoxO3a
TGF-β
IL-6

Question 6

Resistant to all TKIs EXCEPT ponatinib, asciminib

Answer 6

T315I mutation

Question 7

MC symptoms

Answer 7

Fatigue, malaise (anemia)

Early satiety, LUQ pain, abdominal fullness (splenomegaly)

Weight loss (high tumor burden)

Question 8

Symptoms during accelerated or blastic phase

Answer 8

• Fever
• Severe fatigue
• Marked weight loss
• Bone/joint pain
• Infections
• Bleeding or thrombosis

Question 9

MC physical findings in AML

Answer 9

splenomegaly: most common (20–70%)

Question 10

Blasts in CML

Answer 10

≤5% = chronic phase

≥15% = accelerated phase

Question 11

Classic Criteria of Accelerated Phase in CML

Answer 11

• ≥15% blasts
• ≥30% blasts + promyelocytes
• ≥20% basophils
• Clonal evolution
• Platelets <100 × 10⁹/L (non-therapy related)

Question 12

Criteria of Blastic Phase

Answer 12

≥30% marrow or blood blasts
OR
extramedullary blast proliferation

Question 13

Most Important Predictor of Survival in CML

Answer 13

Complete Cytogenetic Response (CCyR)

CCyR ≈ near-normal life expectancy

Question 14

TKI Generations

Answer 14

1st: Imatinib

2nd: Dasatinib, Nilotinib, Bosutinib

3rd: Ponatinib

Novel: Asciminib (myristoyl-site inhibitor)

Question 15

TKI effective for all phases EXCEPT blastic phase

Answer 15

Nilotinib (Tasigna)

Question 16

Optimal TKI if T315I mutation
Failure of ≥2 tyrosine kinase
inhibitors

Answer 16

Ponatinib (Iclusig)

Question 17

Failure ≥2 tyrosine kinase inhibitors

Answer 17

Omacetaxine mepesuccinate
(Synribo)

Question 18

TKI that targets ALL PHASES in CML

Answer 18

Imatinib, Dasatinib, Bosutinib

Question 19

TKI that can cause DIABETES, PANCREATITIS, ARTERIO-OCCLUSIVE DISEASE

Answer 19

NILOTINIB