Leukemias

Question 1

What is leukemia?

Answer 1

Malignancy of hematopoietic cells based in the marrow which then often spills out into the blood.

• can be lymphoid or myeloid
• can involve tissues secondarily

Question 2

How can you tell the difference between an acute and a chronic leukemia?

Answer 2

Look at the WBCs in the peripheral blood. If they’re mature, its chronic. If they’re immature (blasts) then its acute.

Question 3

Does acute leukemia require rapid treatment?

Answer 3

Yup

Question 4

What are the two types of acute leukemia?

Answer 4

Acute lymphoblastic leukemia

Acute myeloid leukemia

Question 5

AML pathogenesis

Answer 5

Mutation(s) that block maturation of myeloid precursors. These precursors build up in the bone marrow and start spilling out into the blood.

Question 6

AML clinical presentation

Answer 6

Findings are related to anemia, neutropenia, and thrombocytopenia. Fatigue, pallor, weakness, infection, fever, bleeding, bruising, and petechiae

Question 7

AML workup (bone marrow, peripheral blood, etc)

Answer 7

Bone marrow: increased blasts (>20% is diagnostic). Usually hypercellular but can be normal or hypocellular depending on patient’s age.

Peripheral blood: increased WBC, blasts (with Auer rods!), thrombocytopenia

Histochemistry: MPO+, CD34, CD 33, CD13,

Question 8

AML treatment

Answer 8

Induction with high dose chemo followed by several rounds of chemo or HSCT

Question 9

I say Auer rods, you say….

Answer 9

AML!

Question 10

I say gingival hyperplasia, you say….

Answer 10

Monocytic AML

Why? Because monocytes keep doing what they do. They leave the blood and go to the tissues to become macrophages. Because they’re not differentiated though, they build up there, leading to hyperplasia.

Question 11

APL pathogenesis

Answer 11

t(15;17) leads to the PML-RARalpha fusion gene. RARalpha is involved in the process of normal granulocytic differentiation. This process is blocked in with the PML-RARalpha fusion, blocking differentiation of myelocytes.

Question 12

What do we have here?

Answer 12

Auer rods!

Question 13

How does APL present?

Answer 13

With leukopenia, few or no circulating blasts, and DIC.

Question 14

How does APL lead to DIC?

Answer 14

The granules contain procoagulants. When the cells rupture in tumor lysis syndrome, these spill out into the blood, resulting in DIC.

Question 15

APL treatment

Answer 15

ATRA (all trans retinoic acid) “unblocks” differentiation and allows the cells to mature

Question 16

CML clinical presentation

Answer 16

Fatigue, weakness, weight loss, anorexia, occasionally abdomial discomfort/fullness due to splenomegaly

Question 17

CML workup (peripheral blood, bone marrow, etc)

Answer 17

Peripheral blood: Elevated WBC with granulocytes in different stages of differentiation, including some blasts. Anemia. Basophilia.

Bone marrow: overgrowth of granulocytic and megakaryocytic precursors

Question 18

CML pathogenesis

Answer 18

t(9;22) aka the Philadelphia chromosome.

This gives rise to the BCR-ABL gene. This creates a constituitively active tyrosine kinase thatactivates the RAS, JAK-STAT, and PI-3K/AKT pathways

Question 19

What happens if CML isn’t treated?

Answer 19

It progresses to AML and/or a blast crisis

Question 20

CML treatment

Answer 20

Imatinib.

• Can lead to complete hematologic remission in stable phase CML
• much less effective in accelerated phase or blast crisis

The only true cure is an allogenic stem cell transplant

Question 21

Answer 21

Bone Marrow AML

Question 22

From what disease is this CBC?

Answer 22

AML (taken from Day 8 Case 3)

Question 23

From what disease is this CBC?

Answer 23

CML (taken from Day 8 Case 4)

Question 24

Answer 24

CML Bone Marrow

Question 25

Answer 25

CML peripheral blood smear