Myelodysplastic Syndrome & Myeloproliferative Neoplasms II

Question 1

CML blood cell counts and marrow findings:

Answer 1

blood:
- leukocytosis due to neutrophilia
- WBC 12,000-1,000,000
- inc basophils and platelets

marrow:
- markedly hypercellular marrow due to a granulocytic hyperplasia
- many small megakaryocytes with round, non-lobated nuclei

Question 2

CML usual cytogenic and molecular abnormalities:

Answer 2

BCR-ABL1 gene fusion. In the majority of cases, this fusion results from a translocation (9;22)(q34;q11.2), with the resultant BCR-ABL1 fusion gene being located on the derivative chromosome 22, which is referred to as the Philadelphia chromosome

Question 3

PV blood cell counts and marrow findings:

Answer 3

Blood cell counts: increase in RBC mass (erythrocytosis), usually accompanied by increased neutrophils and platelets
Marrow findings: the bone marrow showing trilineage hyperplasia. Bone marrow biopsy also typically shows clusters of large, bizarre megakaryocytes

Question 4

PV usual cytogenic and molecular abnormalities:

Answer 4

Nearly all cases of PV contain a mutation of the JAK2 gene encoding the JAK2 cell signaling protein. Most contain the V617F point mutation

Question 5

PMF blood cell counts and marrow findings:

Answer 5

Blood: proliferation of the granulocytic and megakaryocytic lineages, with eventual progression to myelofibrosis

Marrow: hypercellular, megakaryocytes frequently large and bizarre, and present in clusters; reticulin fibers

Question 6

PMF usual cytogenic and molecular abnormalities:

Answer 6

Mutations of JAK2 can be found in around 50% of cases of PMF.

Question 7

ET blood cell counts and marrow findings:

Answer 7

Blood cell counts: marked thrombocytosis
Marrow findings: no granulocytic hyperplasia in the marrow (the marrow is usually normocellular in ET), and the clustered atypical megakaryocytes in the marrow are even larger and more bizarre than in PMF

Question 8

ET usual cytogenic and molecular abnormalities:

Answer 8

Like PMF, mutations of JAK2 can be found in around 50% of cases of ET.

Question 9

Explain why there is a need for a second and third generation of protein tyrosine kinase inhibitors (PTKIs)

Answer 9

Much like bacteria developing resistance to antibiotics, the PTKIs effectively select from new subclones against which the PTKI is not effective, for reasons such as mutation of the PTKI binding site

Question 10

Recall the most common method of death attributable to disease in polycythemia vera (PV) patients, and list 3 sites where thrombosis should always make one consider the possibility of PV

Answer 10

The most serious complications of PV are the predilection for venous or arterial thrombosis, which occurs in around 20% of patients, and can present as DVT, myocardial ischemia, stroke, or other thrombotic event. The possibility of PV should always be considered in a patient with thrombosis of the mesenteric vein, portal vein, or splenic vein

Question 11

Recall the (somewhat archaic) most common treatment for PV

Answer 11

Mainstays of therapy are serial phlebotomy (bloodletting) and aspiring therapy, to decrease the risk of clots.

Question 12

Describe findings that might be seen in a peripheral blood smear of a patient with leukoerythroblastosis and how these findings relate to patients with marrow fibrosis

Answer 12

The peripheral blood shows a picture known as leukoerythroblastosis, where there are increased immature granulocytes (myelocytes, metamyelocytes) and increased immature nucleated red blood cells present. In addition, there are many tear drop-shaped red blood cells (dacrocytes).

-Why? = Bone marrow with significant reticulin fibrosis, with loss of much of the marrow space. This may result in hematopoiesis being present within the marrow sinusoids, so-called intramedullary extramedullary hematopoiesis