Myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs):

These conditions can also be referred to as myeloproliferative disorders (MPD), they’re the same thing. MPNs generally refers to an over proliferation of a mature myeloid cell line. There are three main types, CML (too many mature granulocytes), polycythemia vera (too many mature RBCs), and essential thrombocythemia (too many mature platelets). These conditions (which have the worst names!) will typically present with an elevated to extremely elevated WBC count, increased platelet count, and peripheral cell or bone marrow blasts but <10%. They are also more likely to present with increased organ sizes (organomegaly) due to the cells chronically infecting organs like the liver and spleen. These conditions have a much slower onset in comparison to AML.

Chronic myeloid leukemia (CML):
Chronic myeloid leukemia is an increase in mature and immature granulocytes (neutrophils, basophils, eosinophils). Diagnosis can be confirmed by the chromosomal translocation t(9:22). The translocation transfers a piece of chromosome 9 to 22 and a piece of 22 to 9. Chromosome 9 ends up with a longer piece and chromosome 22 ends up with a shorter piece. This short chromosome 22 is known as the Philadelphia chromosome.

The translocation causes the ABL1 gene from chromosome 9 to combine with the BCR gene from chromosome 22. This fusion gene codes for a tyrosine kinase protein that causes rapid cell division.

Nerdy Note
The Philadelphia chromosome got its name from the city it was discovered in. In 1959, two researchers, David Hungerford and Peter Nowell, discovered the chromosome which became the first chromosomal abnormality associated with a specific type of cancer.

Polycythemia Vera (PV):
Polycythemia Vera is defined by uncontrolled proliferation of erythroid, granulocytic, and megakaryocytic cells; however, it is mostly associated with increased erythroid cells (red blood cells). The WHO has recently revised its criteria for PV because it was perhaps being underdiagnosed. There are three major criteria:

1. Hemoglobin > 16.5 g/dL (men), >16.0 g/dL (women); this was formerly 18.5 and 16.5 respectively, or a hematocrit > 49% (men), >48% (women), or an increased red cell mass.

2. Bone marrow biopsy showing increased erythroid, granulocytic, and megakaryocytic cell lines.

3. Presence of JAK2 V617F or JAK2 exon 12 mutation.

The JAK2 gene codes for a protein that is thought to be highly involved in cell proliferation. The mutation causes this gene to overproduce leading to the overproduction of cells.

Essential thrombocythemia (ET):
Essential thrombocythemia is similar to PV except it only involves the megakaryocyte lineage. It causes a dramatic increase in platelets that have an abnormal function (zombie platelets!). There are four major criteria for ET.

1. Platelet count >450 x 10^3/uL (normal range is 150-450)

2. Bone marrow biopsy showing increased megakaryocyte cell lines with no increase in erythroid and granulocytic cell lines.

3. Not meeting WHO criteria for BCR-ALB1+ CML, PV, or similar diseases.

4. Presence of JAK2, CALR, or MPL mutation.

Now we’ve got the basics down for the myeloid lineage. Let’s jump over to the lymphoid side.