PROMYELOCYTE: CHARACTERISTICS, FUNCTIONS AND PATHOLOGIES - BIOLOGY - 2025

The promyelocytes are hematopoietic progenitor cells of a special class of blood cells known as granulocytes (neutrophils, basophils and eosinophils), which belong to the myeloid lineage of blood cells and are included in the group of white blood cells.

Blood is a liquid connective tissue specialized in the transport of oxygen, nutrients and waste. It is distributed throughout the body and is composed of cellular and non-cellular elements.

Photograph of a promyelocyte (Source: Bobjgalindo via Wikimedia Commons)

Its cellular components include erythrocytes or red blood cells, leukocytes or white blood cells, megakaryocytes, platelets and mast cells, which are produced throughout the life of an organism through a process known as “hemopoiesis”.

During hemopoiesis, a group of pluripotent stem cells in the bone marrow multiply and give rise to progenitor cells of two lineages known as the myeloid lineage (colony-forming unit of the CFU-S spleen) and the lymphoid lineage (lymphoid lineage). colony-forming CFU-Ly lymphocytes).

Two groups of unipotential progenitor cells originate from the myeloid lineage (which multiply to give rise to a single cell line). One gives rise to granulocytes / macrophages and the other to megakaryocytes / erythrocytes.

The group of granulocyte / macrophage progenitor cells divides, in turn, to form four cell lines corresponding to eosinophils, basophils, neutrophils, and monocytes. Promyelocyte is the name given to the precursor cells of the first three types of cells.

Formation of granulocytes

Granulocytes are each derived from a specific group of unipotential progenitor cells, with the exception of neutrophils, which are derived from bipotential cells (which are capable of producing two separate cell lines).

These progenitor cells are descended from a pluripotential stem cell, which is the first link in the myeloid lineage and is known as the colony-forming unit of the spleen or CFU-S. Eosinophils and basophils come from precursors that are known as CFU-Eo and CFU-Ba, respectively.

Neutrophils, as mentioned, come from a bipotential cell line, known as CFU-GM (granulocyte / monocyte), which is subsequently divided into the CFU-G cell line (from neutrophils) and the CFU-M line (from neutrophils). monocytes).

Both the CFU-G progenitor cells and the CFU-Eo and CFU-Ba divide and give rise to the first precursor cell known as the myeloblast. Myeloblasts are identical to each other, regardless of the cell line they come from.

Promyelocytes arise from the mitotic division of myeloblasts from the three cell lines, that is, both from the progenitors of eosinophils and basophils and from neutrophils. These divide again and form myelocytes.

Myelocytes divide by mitosis and form metamyelocytes, which progressively differentiate to form the mature cells of each cell line.

The whole process is modulated by different molecular elements and growth factors, which are what dictate the progress from one stage to the next and which are essential during cell maturation and differentiation.

characteristics

As in the case of myeloblasts, it is not possible to distinguish between promyelocytes that come from any of the three cell lines, since they are identical.

Regarding morphology, it is known that promyelocytes are large cells and that their diameter varies between 18 and 24 microns. They have mitotic capacity, that is, they can divide by mitosis.

They have a round or semi-oval nucleus that stains a reddish-blue color and where a delicate chromatin pattern with one or two nucleoli can be appreciated. At this stage, the beginning of the formation of indentations of the nuclear envelope characteristic of granulocytes is observed.

When compared with myeloblasts, their precursor cells, promyelocytes have a greater accumulation of heterochromatin, which is what is seen as the "chromatin pattern" and which is not evident before this stage.

In its bluish cytoplasm is a rough endoplasmic reticulum associated with a prominent Golgi complex, large numbers of active mitochondria, and lysosomes larger than 0.5μm in diameter. Cytoplasmic vesicles are not observed in the cell periphery.

During granulopoiesis (formation of granulocytes), promyelocytes are the only cells that produce azurophilic granules (primary granules).

These are nonspecific granules that appear to have activities similar to those of lysosomes, since they contain abundant concentrations of acid hydrolases, lysozymes, proteins with bactericidal activity, elastases and collagenases.

Features

The main function of promyelocytes is to serve as precursor cells for eosinophilic, basophilic, and neutrophilic granulocytic cell lines.

Since it is in this type of cell the only one where azurophilic or nonspecific granules originate and accumulate, these cells are essential for the formation of granulocytes.

It is important to remember that the three classes of granulocytic cells, i.e., eosinophils, basophils and neutrophils, have critical roles in the body's first line of defense against foreign agents, against tissue damage, during parasitic infections and allergic and hypersensitive reactions., among others.

Pathologies

In some acute leukemias, some abnormalities in the promyelocytes have been detected by flow cytometry, such as the overexpression of CD 13, CD 117 and CD33, and the absence or under expression of the CD15 marker.

These have been important advances in the study of the immunophenotype of some leukemias, especially M3 myeloid leukemia (acute promyelocytic leukemia).

-Acute promyelocytic leukemia (M3)

It is a type of myeloid leukemia. This pathology was discovered by Hillestad in 1957 but its genetic origin was described in 1970.

In this pathology, promyelocytes present genetic abnormalities (APL-RARα gene) associated with the rupture of nuclear bodies. This prevents the cell from maturing and continuing its differentiation process.

Therefore, the cell stays in that phase. Furthermore, genetic abnormalities also influence the inhibition of apoptosis. That is why the cells do not die and accumulate in the bone marrow, being inevitable that they go out into the circulation. All this aggravates the picture.

It causes severe bleeding and infections, fever, paleness, weight loss, fatigue, loss of appetite, among others.

Treatment

Fortunately, these abnormal cells have receptors for -alpha-trans-retinoic acid or tretinoin, and when this drug is used as a treatment, it promotes the differentiation of promyelocyte to myelocyte, giving very satisfactory results.

Concomitant platelet transfusions, administration of arsenic trioxide (ATO) and anthracycline chemotherapy can be included, although the latter is cardiotoxic.

To monitor the disease and see if the treatment is working, laboratory tests such as a bone marrow biopsy and complete hematology should be performed.

After remission, the patient must continue a maintenance treatment for 1 year to avoid relapses.

Diagnosis

In promyelocytic leukemia, promyelocytes change their morphology. They present with a misshapen nucleus that may have irregular borders or have abnormal lobulations. They present abundant Auer bodies, which is pathognomonic for this pathology.

There is also an accentuation of azurophilic granules (hypergranular variant). However, there is a variant that has very fine granulations (microgranular), almost imperceptible under the light microscope.

There are monoclonal antibodies to the APL-RARα receptor that are used to make the diagnosis. On the other hand, these cells stain positive for CD33, CD13, and sometimes CD2. While it gives negative staining for CD7, CD11b, CD34 and CD14.

Chronic and acute myeloid leukemia

This pathology usually occurs with only 10% presence of blasts and promyelocytes in peripheral blood smears. It is more common in adults but children can also be affected.

This disease progresses slowly but can suddenly become acute. If it becomes acute, the percentage of immature cells increases. Acute leukemias are more aggressive and therefore more difficult to treat.

References

1. Despopoulos, A., & Silbernagl, S. (2003). Color Atlas of Physiology (5th ed.). New York: Thieme.
2. Di Fiore, M. (1976). Atlas of Normal Histology (2nd ed.). Buenos Aires, Argentina: El Ateneo Editorial.
3. Dudek, RW (1950). High-Yield Histology (2nd ed.). Philadelphia, Pennsylvania: Lippincott Williams & Wilkins.
4. Gartner, L., & Hiatt, J. (2002). Text Atlas of Histology (2nd ed.). Mexico DF: McGraw-Hill Interamericana Editores.
5. Johnson, K. (1991). Histology and Cell Biology (2nd ed.). Baltimore, Marylnand: The National medical series for independent study.
6. Kuehnel, W. (2003). Color Atlas of Cytology, Histology, and Microscopic Anatomy (4th ed.). New York: Thieme.
7. Ross, M., & Pawlina, W. (2006). Histology. A Text and Atlas with correlated cell and molecular biology (5th ed.). Lippincott Williams & Wilkins.