General characteristics and pathogenesis
The development of this group is based on damage to a multipotent hematopoietic stem cell, leading to clonal proliferation of one or more myelopoiesis lineages. The most important difference between these conditions and acute leukemias is the preservation of the ability of clonal cells to differentiate into mature forms.
Clinical and morphological manifestations affect the blood system and internal organs:
- Hepatosplenomegaly develops, which is directly caused by processes of extramedullary hematopoiesis.
- An increase in formed elements, including leukocytosis and thrombocythemia, is recorded in the peripheral blood.
- A marked increase in the number of megakaryocytes and the formation of fibrosis are observed in the bone marrow tissue.
Classification of main nosologies
The pathology includes several independent nosological forms differing in clinical and genetic features:
- Chronic myeloid leukemia (CML), Ph+ — a form associated with the Philadelphia chromosome marker.
- Chronic neutrophilic leukemia.
- Chronic eosinophilic leukemia, also known as hypereosinophilic syndrome.
- Chronic idiopathic myelofibrosis.
- Polycythemia vera, or erythremia (Vaquez disease).
Focus on Chronic Myeloid Leukemia
Among all nosologies, CML with the presence of the Philadelphia chromosome deserves special attention. This genetic alteration is a specific chromosomal rearrangement.
- Cytogenetics: translocation t(9;22)(q34;q11).
- Molecular marker: formation of the bcr/abl chimeric gene.
It is this genetic marker that serves as a key diagnostic criterion for verifying this form among other myeloproliferative disorders.
Briefly: answers to topical questions
What bone marrow changes are characteristic of myeloproliferative neoplasms?
Myeloproliferative neoplasms are characterized by bone marrow changes associated with clonal proliferation of one or more myelopoiesis lineages while maintaining the ability of cells to differentiate.
The following may be observed in the bone marrow:
- Increased number of megakaryocytes.
- Development of fibrosis.
- In polycythemia vera — panmyelosis, i.e., hypercellularity of the erythroid, granulocytic, and megakaryocytic lineages.
What peripheral blood changes are typical for myeloproliferative neoplasms?
Typical peripheral blood changes in myeloproliferative neoplasms include an increase in one or more types of formed blood elements.
The main manifestations include:
- Leukocytosis.
- Thrombocythemia.
- An increase in one or more types of formed blood elements.
- Chronic myeloid leukemia is characterized by the eosinophil-basophil association — a simultaneous increase in the number of eosinophils and basophils.
What stages are distinguished in the clinical course of chronic myeloid leukemia?
Three successive stages are distinguished in the clinical course of chronic myeloid leukemia.
- Chronic phase — a monoclonal phase lasting from 3 to 5 years, in which the blast count is 1–3%.
- Accelerated phase — an intermediate stage of progression.
- Blast crisis (blast transformation) — a terminal stage characterized by decreased cell differentiation, polyclonal proliferation, and high treatment resistance.
What macroscopic and microscopic changes occur in the spleen in chronic myeloid leukemia?
Chronic myeloid leukemia develops splenomegaly associated with extramedullary hematopoiesis and leukemic infiltration.
- Macroscopic changes: spleen mass may exceed 3 kg, consistency is dense, cut surface is mottled. Infarction zones are possible due to vascular obliteration by accumulations of tumor cells — leukemic thrombi.
- Microscopic changes: red pulp is engorged with leukemic cells, lymphoid follicles are replaced by massive proliferation of leukemic cells. Leukemic infiltrates may be located along the interstitium, around vessels, and in their walls; infiltration is often diffuse.
What genetic mutation is a specific marker of polycythemia vera?
A specific genetic marker of polycythemia vera is a mutation in the JAK2 gene. According to WHO diagnostic criteria, confirmation of the diagnosis as a major criterion requires the detection of the JAK2 V617F mutation (also designated as V617ZF) or the presence of a mutation in exon 12 of the JAK2 gene.
What are the main complications and causes of death characteristic of polycythemia vera?
The main causes of death in polycythemia vera are complications associated with arterial hypertension and thrombosis. Characteristic complications include:
- Thrombotic lesions — myocardial infarction, ischemic stroke, pulmonary infarction, and gangrene of the fingers and toes.
- Tumor progression — transformation of the disease into myelofibrosis or acute myeloid leukemia.
"Myelo-PRO-liferation — cells PRO-ceed to differentiate" (the main difference from acute leukemias).
Class and exam questions
What is the main mechanism underlying the development of myeloproliferative neoplasms?
It is based on malignant transformation of a multipotent hematopoietic stem cell, leading to clonal proliferation of one or more myelopoiesis lineages.
What key feature distinguishes these disorders from other leukemias?
The key feature is that clonal cells fully retain their ability to differentiate.
What causes hepatosplenomegaly in these pathologies?
Enlargement of the liver and spleen is due to the development of foci of extramedullary (extraosseous) hematopoiesis.
Which genetic marker is characteristic of chronic myeloid leukemia?
It is characterized by the presence of the Philadelphia chromosome resulting from the t(9;22)(q34;q11) translocation with the formation of the bcr/abl chimeric gene.
What else to study on this topic
- Features of the t(9;22) translocation and function of the bcr/abl protein
- Morphological diagnosis of bone marrow fibrosis
- Pathogenetic mechanisms of polycythemia vera
- Differential diagnosis of primary myelofibrosis
- Clinical manifestations of extramedullary hematopoiesis
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