Acute Leukemia

Question 1

What is the global picture idea to acute leukemia?

Answer 1

There is a disruption in the step wise fashion in maturing blood cells. This causes a build up of stem cells or the blast cells.

Question 2

How do we define acute leukemia?

Answer 2

Accumulation of greater than 20% of blasts.

Question 3

What is the big picture MOA of disruption by the accumulation?

Answer 3

The overwhelming number of blasts hinder normal hematopoietic. So clinically, it can present as anemia/fatigue if RBCs aren’t being produced, thrombocytopenia/bleeding if platelets arent being produced, and neutropenia/infection.

Question 4

What do all the blasts do once they build up? What are three identifying features of the blast?

Answer 4

They will pour out into the blood causing a high WBC count.

Large, immature, and a punched out nucleolus.

Question 5

What are the two types of acute leukemia?

Answer 5

Lymphoblastic and myelogenous

Question 6

What is a good definition of acute lymphoblastic leukemia and what is the marker we use to identify these?

Answer 6

Neoplastic accumulation of lymphoblasts, greater than 20%, in the bone marrow.
TdT, which is a DNA polymerase only found in the nucleus of lymphoblasts

Question 7

ALL classically presents in what patient population and what is a high yield association with ALL, but what is the catch?

Answer 7

Children

Down syndrome, but will not arise typically until after 5 years of age.

Question 8

What are the two subtypes of ALL, which one is most common, and are the three markers for the most common one?

Answer 8

B ALL and T ALL
Most common is B
CD 10,19,20

Question 9

Explain the treatment of B ALL and what two things must we make sure to do?

Answer 9

Excellent response to chemotherapy.

Need prophylaxis or independent or custom treatment to testicles and CSF because of their blood barriers

Question 10

Explain the concept of prognosis of B ALL being based on cytogenic abnormalities?

Answer 10

Translocation of 12:21 has good prognosis and more seen in kids
Translocation of 9:22 has a poor prognosis more commonly seen in adults

Question 11

What are the markers for T All?

Answer 11

CD2-8

They do not express cd10

Question 12

How does T ALL usually present and what is the other name for it?

Answer 12

Teenager with a thymic mass

Acute lymphoblastic lymphoma

Question 13

What is the marker for acute myeloid leukemia, how do we identify the marker, and what patient population do we typically see it in?

Answer 13

MPO
Under microscope, there will be crystal aggregates of MPO seen as Auer rods.
50-60

Question 14

Explain how we subclassify AML?

Answer 14

We start with trying to see if there are any cytogenic abnormalities. If there are, we subclassify it by that
If not, then we subclassify it by the lineage of the immature myeloid cell.

Question 15

What is the high yield subtype of AML if we classify it by cytogenic abnormalities? How do we characterize it and what is he problem because of the genetic mutation?

Answer 15

Acute promyelocytic leukemia
Translocation of the retinoic acid receptor from chromosome 17 to 15.
Disruption of the RAR blocks maturation of cells so there is a build up of myeloid blasts.

Question 16

APL is a huge risk for what condition and how do we treat APL?

Answer 16

DIC

ATRA

Question 17

Let’s say we cant subclassify the AML based on cytogenic abnormalities, so we have to on lineage of immature cells, what are the two High Yield ones?

Answer 17

acute monocytic and acute megakaryoblast

Question 18

What do the monoblasts in acute monocytic lack and where in the body do they classically infiltrate?
What do the megakaryoblasts lack in acute megakaryoblastic and what high yield association is there?

Answer 18

MPO and infiltrate the gums

MPO and Down syndrome association

Question 19

Quickly recap and discuss the association acute leukemia has with Down Syndrome?

Answer 19

Down syndrome is highly associated with leukemia. It is associated with ALL in kids over 5 and AML (megakaryoblastic) in kids less than 5.

Question 20

AML can also arise from an alternative pre existing condition. What is that condition, what are two causes, what are 4 clinical/morphological signs, and how do these patients progress?

Answer 20

Myelodysplasia.
Prior exposure to alkylating agents, like chemo, or radiotherapy
Cytogenic, hypercellular bone marrow, abnormal maturation of cells, and increased blasts (but less than 20%)
Most die from infection or bleeding, but some progress to AML