Nature of the neoplastic clone and general triad
The neoplastic clone in leucosis exhibits genetic instability, a tendency toward phenotypic evolution, and impaired cell differentiation. Over time, a transition from monoclonality to polyclonal proliferation may occur, a striking example of which is the blast crisis stage in chronic myeloid leukemia.
All leukemias are characterized by a classic triad of signs:
- Primary involvement of the bone marrow.
- Circulation of neoplastic cells in the peripheral bloodstream.
- Early and widespread metastasis (neoplastic infiltration).
Tissue infiltration can be diffuse (causing significant organ enlargement) and focal (formation of nodules invading the capsule).
Clinical and morphological division: acute and chronic forms
Depending on the degree of differentiation of the neoplastic elements, two main groups are distinguished:
- Acute leukemias: the substrate consists of immature, poorly differentiated blast cells. The disease runs a rapid course, beginning with the malignant transformation of a stem cell, active proliferation of blasts, and replacement of normal bone marrow.
- Chronic leukemias: the substrate is composed of maturing cytic elements derived from committed precursors. The cells partially retain the ability to undergo terminal differentiation.
The number of neoplastic elements in the blood varies, determining the form of the process: leukemic, subleukemic, leukopenic, or aleukemic.
Chronic myeloid leukemia and genetic markers
A prominent representative of chronic forms is chronic myeloid leukemia, which is based on the involvement of a pluripotent stem cell. About 95% of patients have a specific cytogenetic marker — the Philadelphia chromosome (Ph-chromosome), which is formed as a result of a reciprocal translocation between chromosomes 9 and 22: `t(9;22)(q34;q11)`.
As a result, a chimeric BCR-ABL gene is formed, encoding a protein with increased tyrosine kinase activity. This leads to a marked proliferation of the granulocytic lineage and the replacement of fatty bone marrow with juicy grayish-pink or greenish pyoid tissue.
Pathomorphology of internal organs
Systemic infiltration and extramedullary hematopoiesis lead to pronounced changes in parenchymatous organs:
- Spleen: markedly enlarged (mass may exceed 3 kg), dense, mottled on cross-section. The red pulp is filled with neoplastic elements, follicles are replaced, and infarctions frequently occur due to leukemic thrombi.
- Liver: reaches 5–6 kg, sinusoids within the lobules are densely infiltrated with neoplastic cells, and secondary dystrophic changes develop in hepatocytes.
- Lymph nodes: in the early stages, they enlarge insignificantly, are soft, and grayish-red.
Briefly: answers to topical questions
What types of leukemic manifestations are distinguished depending on the number of neoplastic elements in the blood?
Depending on the content of leukocytes and blast cells in 1 µL of peripheral blood, four forms of leukemia are distinguished.
- Leukemic form — tens and hundreds of thousands of cells (total leukocyte count > 30–50 × 10⁹/L), large number of blasts.
- Subleukemic form — no more than 15,000–25,000 cells (total leukocyte count above normal, up to 30–50 × 10⁹/L), large number of blasts.
- Leukopenic form — total leukocyte count below normal, but blast cells are detected in small numbers.
- Aleukemic form — total leukocyte count within normal limits, leukemic cells absent in the blood (detected only in hematopoietic tissue).
What are the diagnostic criteria for the blast crisis stage in chronic myeloid leukemia?
Diagnosis of the blast crisis stage in chronic myeloid leukemia is based on laboratory parameters and clinical presentation. The main laboratory criterion is the detection of more than 20% blasts in the bone marrow and peripheral blood. The stage is characterized by polyclonality (appearance of new non-differentiating subclones) and decreased cell maturation.
- rapid deterioration of condition;
- high resistance to treatment;
- rapid enlargement of the spleen (often with organ infarctions);
- fever and ossalgia (bone pain);
- appearance of dense leukemic infiltrates in the skin;
- enlargement of lymph nodes.
Syndrome triad: A-I-H (Anemia, Immunodeficiency, Hemorrhagic syndrome). CML stages: Chronic $ ightarrow$ Acceleration $ ightarrow$ Blast crisis (C-A-B).
Class and exam questions
How do acute leukemias differ from chronic ones in terms of morphological substrate?
Acute leukemias are characterized by the predominance of immature, poorly differentiated blast cells. In chronic leukemias, the substrate is represented by maturing cytic elements that partially retain the ability to differentiate.
What is the Philadelphia chromosome and in what disease is it found?
This is an abnormal chromosome formed as a result of the t(9;22)(q34;q11) translocation with the formation of the BCR-ABL gene. It is found in approximately 95% of patients with chronic myeloid leukemia.
What are the main causes of hemorrhagic syndrome in leukemias?
The syndrome is caused by thrombocytopenia due to suppression of the megakaryocytic lineage, liver damage with impaired synthesis of clotting factors, hypoxia of the vascular wall against the background of anemia, and its direct damage by leukemic cells.
What else to study on this topic
- Pathogenesis and cytogenetics of acute myeloid leukemia
- Myelodysplastic syndromes and their morphological features
- Acceleration and blast crisis phases in chronic myeloid leukemia
- Mechanisms of secondary immunodeficiency and ulcerative-necrotic complications development
- Extramedullary hematopoiesis in leukemias
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