AML

Question 1

What syndrome is associated with JMML? What is the typical mutation associated with that syndrome?

Answer 1

Noonan syndrome, PTPN11

Question 2

Updated JMML criteria

Answer 2

LEVEL 1 (all 4 required):

• Splenomegaly,
• Monocytosis >1*10¨9 in PB
• Less than 20% blasts in BM,
• BCR-ABL (-)ve

LEVEL 2 (1 required):

• Somatic mutation of n-ras, k-ras, PTPN11
• NF1
• Germline mutation of CBL

LEVEL 3 (2 required if no level 2 criteria)

• Increase in myeloid precursors
• Elevated Hgb F
• Hyperphosphorylation of STAT5
• Hypersensitivity to GM-CSF
• Monosomy 7, or other clonal abnormalities

Question 3

Transient abnormal myelopoiesis:

• Incidence in patient with Down syndrome?
• % of patients with TAM who will develop AMKL

Answer 3

10%

20-30%

Question 4

Cytogenetics associated with transient abnormal myelopoiesis;
Cytogenetics associated with transformation into AMKL

Answer 4

GATA1

+trisomy 8 , TP53

Question 5

Natural history of transient myeloproliferative disorder associated with Down syndrome

Answer 5

Spontaneous regression in majority of cases within 3 months; minority of patients can develop life-threatening conditions
(hyperviscosity, hydrops fetalis, cardiac failure, massive organomegaly with respiratory compromise, severe hepatic dysfunction, etc.)

Question 6

Common cytogenetic abnormality in non-DS related AMKL

Answer 6

T(1;22)

Question 7

Genes associated with familial MDS/AML syndrome (3)

Answer 7

CEPBA: mostly AML, very penetrant
GATA2: involved in blood, vascular and lymphatic development; not full penetrant, associated as well with mono-MAC syndrome
RUNX1: also associated with thrombocytopenia and platelet dysfunction

Question 8

What is the recommended follow up after TAM?

Answer 8

• Clinical assessment, CBC/diff q1 month until 3 m.o. or normalization of counts
  After normalization of blood counts
• Clinical assessment, CBC/diff, blood smear q3 months until 4 y.o.

Question 9

What is the molecular signature of APML?

Answer 9

PML-RARa

Question 10

What symptoms are seen in differentiation syndrome?

Answer 10

Fever
Respiratory distress, hypoxia, pulm infiltrates
Pleural or pericardial effusion, peripheral edema, weight gain, congestive heart failure, hypotension
Erythematous rash
Acute kidney injury

Question 11

What is the management of differentiation syndrome?

Answer 11

• Dexamethasone to be started promptly
• Hold offending agents (ATRA, arsenic)
• Supportive care, including hydration and furosemide if needed