Promyelocytic leukaemia (PML)

• What is Promyelocytic Leukaemia (PML)?
• Statistics
• Risk Factors
• Progression
• Symptoms
• Clinical Examination
• How is it Diagnosed
• Prognosis
• Treatment
• References

What is Promyelocytic Leukaemia (PML)?

Promyelocytic leukaemia is a malignancy of the bone marrow in which there is a deficiency of mature blood cells in the myeloid line of cells and an excess of immature cells called promyelocytes. Promyelocytic Leukaemia is considered to be a form of acute myeloid leukaemia (AML). It is hence classified as the M3 variant of acute myeloid leukaemia in the French-American-British (FAB) classification. Bone marrow is found inside most of the bones in the body. By adulthood, a large proportion of bone marrow has become relatively inactive. Generally speaking, it is the marrow inside the vertebra, ribs and pelvis, which is responsible for producing the blood cells in adults. In times of crisis or when these areas of bone marrow are damaged, marrow activity may switch on in the other bones.
The bone marrow is a collection of cells inside a connective tissue and fatty stroma. Stem cells are the ultimate origin of the other cells. Stem cells differentiate to form 3 main types of ‘progenitor’ cells. Each of these cells is then responsible to produce red cells, white cells and megakaryocytes (which produce platelets). There are a number of proteins, which stimulate production of blood cells. These include erythropoietin, (EPO) granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), Interleukin 3, 5 and 6 (IL-3, IL-5, IL-6). Generally speaking, these proteins interact with receptors on the surface of the primitive bone marrow cells and stimulate them to produce the adult cells.

Statistics

Promyelocytic leukaemia accounts for 5-10% of the total cases of acute myeloid leukaemia. It occurs mainly in young adults below the age of 40.

Risk Factors

APL is due to a translocation (an exchange of chromosome material) between chromosomes 15 and 17 which is symbolized t(15;17). The genes involved in the chromosomal translocation are referred to as the promyelocytic leukaemia (PML) gene and the retinoic acid receptor-alpha (RARα) gene.

How is it Diagnosed

A full blood count and film will usually reveal low levels of mature blood cells and high levels of immature cells.

Prognosis

The prognosis of PML depends upon a number of factors including stage at time of diagnosis and white blood cell count. In clinical practice approximately 90% of all patients can achieve complete remission thanks to excellent treatment modalities.

Treatment

The mainstay of treatment for PML is all-trans-retinoic acid (ATRA). This drug promotes mature blood cells to form and hence can induce remission in a great majority of patients. This is often used in conjunction with chemotherapy. For patients who do not respond sufficiently to this treatment or relapse following remission, arsenic trioxide can be used.² Information on other types of leukaemia:

• Chronic Myeloid Leukaemia
• Multiple myeloma
• Myelodysplastic syndrome
• Chronic cymphocytic leukaemia
• acute lymphoblastic leukaemia
• Acute myeloid leukaemia

References

1. Kumar, Vinay, Abul Abbas, and Nelson Fausto. Robbins and Cotran Pathologic Basis of Disease, 7th ed. (2004).
2. Sacher, Ronald A. and Richard A. McPherson. Wildman’s Clinical Interpretation of Laboratory Tests, 11th ed. (2000).