Myelodysplastic Syndrome/Myeloproliferative Neoplasms

Question 1

MDS mechanism

Answer 1

Marrow replaced by malignant clone. Ineffective hematopoiesis, cells often die before leaving marrow

Question 2

Primary (idiopathic) MDS age of onset

Answer 2

50ish

Question 3

MDS diagnosis

Answer 3

Persistent peripheral cytopenia. If unilinear, usually anemia. If neutropenia/thrombocytopenia, usually not MDS.

1) morphologic dysplasia
erythro: moth-eaten chromatin, ring sideroblasts (iron-loaded mitochondria that stain w/ Prussian blue)
granulo: hypogranular, pince-nez nuc. segmentation
megakar: small, hypolobated nuclei
2) increased myeloblasts, <20% of cells
3) clonal cytogenic abnormality

Question 4

Secondary MDS

Answer 4

Vitamin deficiency, toxin exposure, virus, certain drugs

Question 5

MDS classifications

Answer 5

Low grade: myeloblasts not elevated

High grade: myeloblasts elevated, still <20% of cells

Question 6

Myeloproliferative neoplasms

Answer 6

Neoplastic clone–>increased blood cell #
increase in 1 or more cell type w/ increased marrow cellularity
organomegaly
marrow fibrosis, failure

Question 7

Chronic Myelogenous Leukemia CML

Answer 7

t(9;22) defines disease
Philly chromosome. BCR-ABL fusion–> increased tyrosine kinase activity, increased cell growth.
40-60yo diagnosis, often incidental finding
basophilia is characteristic

Question 8

CML phases

Answer 8

1) chronic: basophilia, neutrophilia, hypercellular BM
2) blast: >20% blasts in BM.
CML may proceed through intermediate, accelerated phase to acute leukemia
mutation is in the HSC, so when the condition becomes acute, the HSC can lead to overproduction of lymphoblasts or myeloblasts! ALL/AML

Question 9

t(9;22)

Answer 9

210kD BCR-ABL fusion protein (as opposed to 190kD in ALL

increased tyrosine kinase activity leads to increased proliferation.

Question 10

CML treatment

Answer 10

protein tyrosine kinase inhibitor (PTKI)
-Gleevec/imatinib
some patients are resistant due to mutated binding site

Question 11

Polycythemia Vera

Answer 11

increased RBC mass (mature cells)
usually also increased neuts/platelets–trilineage hyperplasia
JAK2 gene activating mutation
treat w/ blood transfusions, asprin to prevent clotting

Question 12

secondary erythrocytosis

Answer 12

in absence of JAK2, increased RBC DUE TO SMOKING (carboxy Hb, chronic hypoxia (altitude), Hb disorders)

Question 13

PV manifestations

Answer 13

Initially, hyperviscous blood leading to headaches, disiness, plethora, megaly, pruritus (histimine release from increased mast cells)
chronically, marrow fibrosis
SaO2 is normal, so EPO is decreased due to negative feedback resulting from high crit. In reactive polycythemia, EPO is increased

Question 14

primary myelofibrosis PMF

Answer 14

granulocyte & megakaryocyte hyperplasia
50% JAK2 mutant
pre-fibrotic stage: marrow hypercellularity, excess platelet derived growth factor (leading to fibrosis later), increased neuts and platelets
fibrotic stage: reticulin fibrosis of marrow, decreased blood cell #s, extramedullary hematopoiesis leading to splenomegaly, leukoerythroblastosis due to immature cells in blood, dacrocytes