AML

Question 1

List 2 types of findings that would allow for a diagnosis of AML.

Answer 1

Presence of ≥20% myeloblasts in the marrow and/or peripheral blood

Presence of certain recurrent cytogenetic abnormalities (usually translocations) = AML, regardless of count

Question 2

Recognize an Auer rod, and relate its clinical significance.

Answer 2

Some of the myeloblasts may contain Auer rods, allowing for their identification as myeloblasts by morphology alone

Question 3

Recall the associated prognosis for the 5 recurrent cytogenetic abnormalities for AML listed in the notes, and recall their typical patient populations if one is listed.

Answer 3

t(8;21) RUNX1-RUNX1T1 = relatively good prognosis, young adults
inv(16) CBFB-MYH11 = relatively good prognosis, young adults
t(15;17); PML-RARA = extremely good, watch out for DIC in presentation, any age
t(1;22); RBM15-MKL1 = good prognosis
MLL 11q23: poor prognosis, any age

Question 4

Explain two reasons why it is important to recognize at initial diagnosis that a case of AML is the AML with t(15;17)( aka acute promyelocytic leukemia (APL)) subtype of AML.

Answer 4

1. Recognize right away so the pt doesn’t get standard cehmo which could harm them
2. ## DIC is common (emergency)
3. RARA encodes retinoic acid receptor alpha protein. Signalling through this receptor is required for differentiation past the promyelocyte stage.
   In APL, the PML-RARA fusion protein functions poorly as a retinoic acid receptor. However, adequate levels of signalling activity can be obtained with supraphysiologic doses of all-trans retinoic acid (ATRA)
   Thus, APL patients do not required traditional induction chemotherapy (initial treatment) with the usual chemotherapeutic agents, which have significant rates of morbidity and mortality. They can be treated instead with ATRA and arsenic salts, which have very little morbidity and almost no mortality.
   2) APL is often associated with disseminated intravascular coagulation (DIC), which can be a medical emergency. Thus, identification of the acute leukemia as APL alerts the clinician to the possibility of DIC, and appropriate measures can be taken if necessary.

Question 5

Contrast the 2 main categories of therapy-related AML, and compare their prognosis.

Answer 5

Alkylating/Rad vs. Topo Inhib
2-8yrs 1-2yrs
del 5 or 7* 11q23; MLL
via MDS not via MDS

*along with other abnormalities
Age population = older

Question 6

List 3 molecular markers currently used to predict prognosis in patients with AML with normal karyotype, and know which of these “trumps” the other two as a driving prognostic factor.

Answer 6

FLT3 = bad

NPM1 or CEBPA = good