Myeloproliferative Neoplasms (Final)

Common findings in all MPNs

- Mutation in stem cells

- Increase in 1 or more cell lines

- End in acute leukemia

- Splenomegaly

- Middle-aged adults (mostly)

- Chronic onset

- Overlapping lab results

Chronic Myelogenous Leukemia (CML) is caused by a translocation of the long arm of chromosome ______ to chromosome ______ (Philadelphia chromosome).

9, 22

This causes an increased number of immature ______.

neutrophils

CML S/Sx

- Frequent infection

- Anemia

- Bleeding

- Splenomegaly

- Increased myeloid progenitors in BM, blood, and other tissues

The Philadelphia chromosome produces the ______ gene responsible for making a fusion protein.

BCR-ABL

This fusion protein 210kD BCR/ABL has increased ______ activity involved in signal transduction.

tyrosine kinase

This causes cells to continually proliferate without ______.

differentiation

CML patient peripheral blood will show normal/decreased ______ with the presence of ______.

RBCs, reticulocytes

WBCs will be increased with a ______, along with the increased presence of ______.

left shift, PLTs

In the BM, it will be hypercellular with increased ______ and decreased ______.

granulopoiesis, erythropoiesis

______ can be normal or increased, and there may be ______ cells present.

megakaryopoiesis, pseudo-Gaucher

In CML patients, the spleen and liver will both be ______.

enlarged

______ can be used to treat CML.

Imatinib mesylate (Gleevec)

Imatinib is a synthetic protein that binds to abnormal ______ fusion protein.

BCR/ABL

The goal of CML treatment is ______.

remission

Remission can occur hematologically, creating a normal ______.

CBC/differential

Remission can be cytogenetic, showing absence of the ______.

Philadelphia chromosome

Molecularly, remission will show very decreased/absent ______.

BCR/ABL

Resistance to Imatinib can arise from other ______ in BCR/ABL or in the ATP binding site.

mutation (not t(9;22))

In this case, other ______ inhibitors can be used

tyrosine kinase

EPO production is increased with decreased ______ levels.

oxygen

Relative Polycythemia Vera (PV) is benign, caused by a decrease in ______ volume, not in RBC mass.

plasma

This can be caused by ...

Loss of fluids

(Dehydration, excessive vomiting, etc.)

In the lab, Relative PV shows normal everything, but increased ______.

RBCs

EPO will be ______ in Relative PV.

normal

Secondary PV is a true increase in ______ secondary to other factors.

RBC mass

These other factors can be ...

Altitude changes, smoking, etc.

In the lab, Secondary PV will produce increased ______, ______ and ______.

RBCs, H&H, MCV

In Secondary PV, EPO will be ______.

increased

PV is caused by a mutation in the ______.

pluripotential stem cells (JAK2 V617F)

This causes PSC resistance to ______ and no ______.

apoptosis, differentiation

With PV, what will be increased in the PB?

- H&H

- MCV

- WBCs

- PLTs

In the BM, what will be increased?

- Normoblasts

- Granulopoiesis

- Megakaryopoiesis

- Reticulin

The spleen and liver of PV patients will be ______.

enlarged

PV is s true malignancy that causes a large increase in all ______, especially RBCs.

cell lines

This RBC increase is independent of ______ levels.

EPO

In the lab, PV shows increased levels of ...

- RBCs

- WBCs

- PLTs

- H&H

The BM will be ______ and EPO can be ______.

hyperplastic, variable

The major criteria for PV diagnosis are ...

- Increased Hgb

- Hypercellularity of 3 lineages in BM

- JAK2 mutation (often V617F)

The minor criteria for PV diagnosis is decreased ______.

EPO

Treatment of PV is therapeutic ______ to control HCT under 45%.

phlebotomy

______ can reduce clotting in PV patients.

Aspirin (low dose)

Essential Thrombocythemia (ET) involves increased ______ and ______.

megakaryopoiesis, thrombocytosis

In the peripheral blood, ______ will be decreased and ______ will be increased.

H&H, WBCs

ET is especially characterized by a significant increase in ______.

PLTs

The ______ mutation causes ET in over half the cases.

JAK2 V617F

S/Sx of ET

- Asymptomatic

- Clots or bleeding

Primary Myelofibrosis (PMF) causes hematopoietic cells in the BM to be pushed out by excess ______.

collagen

A sign of this can be the presence of ______ in the peripheral blood (non-specific)

dacrocytes

As a response to PMF, hematopoiesis occurs in other organs such as the ______ and ______.

liver, spleen

In the lab, PMF shows the ______ mutation.

JAK2 V617F

In the PB, ______ will be increased with PMF.

Anisocytosis/poikilocytosis

What else will be present in PMF?

- nRBCs

- Blasts

- Abnormal PLTs/megakaryocytes

H&H and polychromasia can be ______ with PMF.

normal/increased

What PB components can be variable with PMF?

- WBCs

- PLTs

In the BM, you will see increases in ______ in all three cell lines and in ______.

hematopoiesis, myelofibrosis

Similar to previous diseases, enlargement of the ______ and ______ will be seen with PMF.

spleen, liver

Myelodysplastic Syndrome (MDS) common characteristics

- Cytopenia

- Abnormal production

- Bleeding

- Increased infections

- Decreased RBCs

- Splenomegaly

Morphologically, MDS will show ______ and ______.

dyserythropoiesis, dysmyelopoiesis

What will dyserythropoiesis show?

- Oval macrocytes

- Hypochromic microcytes

- Dimorphic RBC population

- Poikilocytosis, basophilic stippling, Howell-Jolly bodies, siderocytes

- Abnormal RBC precursors in BM

- Low Hgb

What will dysmyelopoiesis show?

- Basophilia in mature WBCs

- Abnormal PMN ganules

- Hypo- or hypersegmentation

- Uneven cytoplasm in BM

- Neutropenia

Dysmegakarypoiesis shows ______ PLTs and abnormal granulation.

giant

MDS types

- MDS with Single Lineage Dysplasia

- MDS with Ringed Sideroblasts

- MDS with Multilineage Dysplasia

- MDS with Excess Blasts

- MDS with Isolated del(5q)

- Unclassified

Chronic Myelomonocytic Leukemia (CMML) causes increased ______.

myelocytes/monocytes

The BM of a CMML patient will show increased ______.

blasts