Hematological malignancies
Now onto the myeloid stem cells disorders. Let’s start with the myeloproliferative
neoplasms.
Myeloproliferative neoplasms are characterized by an increased proliferation of myeloid stem
cells. Differentiation into mature cells is usually preserved.
The three cell lines of myelopoiesis are the red blood cells, the platelets, and the granulocytes.
More or less, there is a myeloproliferative neoplasm for each cell line:
There is an increased production of red blood cells in polycythemia vera.
There is an overproduction of platelets in essential thrombocythemia.
And granulocyte formation is uncontrollably increased in chronic myeloid leukemia.
However, these examples serve only as a starting point, because more than one cell line may
be affected in these disorders.
One additional myeloproliferative neoplasm is myelofibrosis. Typically, myelofibrosis
involves an initial increase in platelets and granulocytes. The cells in the bone marrow,
particularly the megakaryocytes, also show dysplastic changes. The origin of the name
myelofibrosis is due to its late phase, when the bone marrow burns out and becomes fibrotic
over time.
In addition to the four previously mentioned examples, the group of myeloproliferative
neoplasms includes other rare disorders. However, these will not be mentioned here. The WHO
classification system for myeloproliferative neoplasms provides a detailed overview of
these rare forms.
We just mentioned chronic myeloid leukemia and would like to reflect on several aspects
of this disorder.
In chronic myeloid leukemia, there is an increased proliferation of the granulocyte cell line.
As the cells are still in the process of differentiation, the blood count shows cells from all intermediate
stages, from myeloblasts to segmented granulocytes. So, the blood smear of a patient with chronic
myeloid leukemia shows neutrophils in all stages of maturation. This is important to
distinguish chronic myeloid leukemia from the differential diagnosis of acute myeloid
leukemia, in which there are simply an abundance of blast cells in the blood, but no intermediate
stages. This latter phenomenon is termed leukemic hiatus or gap, which results from the maturation
arrest of blast cells.
Leukemic hiatus is not a feature of early-stage chronic myeloid leukemia. Instead, chronic
myeloid leukemia classically progresses in three phases, with a leukemic-like phase at
the end. The initial phase is the chronic phase, which then transforms through further
chromosomal alterations into the accelerated phase. The terminal phase of chronic myeloid
leukemia is the blast crisis, which is characterized by an increase in blast cells, with a clinical
picture similar to that of acute leukemia.
Now onto the myelodysplastic syndromes. They can be best described as a bone marrow dysfunction
leading to dysplastic cells. One disorder belonging to this group is refractory anemia.
It is characterized by an ineffective erythropoiesis, which results in a decreased number of red
blood cells. As opposed to other anemias, it does not respond to treatment with vitamin
B12, folic acid, or iron; hence the name refractory.
Myelodysplastic syndromes may transform into acute leukemia over time. This is evident
in an increase in the percentage of blast cells. Here are two examples: The first is
refractory anemia with excess blasts, or RAEB. If the percentage of blast cells continues
to increase, it is referred to as transformation, that is, the disorder progresses into acute
leukemia. The disorder is then termed refractory anemia with excess blasts in transformation.
The current WHO classification system for myelodysplastic syndromes comprises eight
different disorders. However, we’re going to remain with these three examples derived
from refractory anemia, and allow particular emphasis on understanding the relationships
rather than the details of each of the eight myelodysplastic syndromes.