Causes and mechanisms of neoplastic transformation
The basis of hemoblastosis development is not the inheritance of the disease itself, but the transmission of genome instability in hematopoietic cells — reduced chromosomal resistance to mutagens. Key risk factors include:
- DNA repair gene expression anomalies: cells are less efficient at eliminating mutations, which enhances the effect of carcinogens.
- Iatrogenic factors: the use of cytostatics and immunosuppressants repeatedly increases the risk of acute leukemias.
- Ionizing radiation: radiation therapy and exposure with a latent period of 5–10 years.
- Smoking: increases the likelihood of acute myeloid leukemia by 1.3–2 times.
- Chronic antigenic stimulation: excessive burden on the immune surveillance system predisposes to lymphoid neoplasms.
Tumor progression and signs of atypia
Genome instability triggers a cascade of changes, including apoptosis, telomerase activation, and oncogene expression. Mutant subclones emerge, among which the best-adapted survive during intra-tumoral selection.
This explains the progressive (unrelenting) course of the disease, the generalization of the process, and the tumor's escape from cytostatic therapy.
In the bone marrow, there is a simultaneous coexistence of normal and tumor hematopoietic lineages, as well as a "rejuvenation" of the cellular composition. Severe syndromes develop in the peripheral blood due to the expansion of tumor cells:
- Anemia due to the suppression of erythropoiesis.
- Thrombocytopenia resulting from the suppression of the megakaryocytic lineage.
- Hemorrhagic syndrome against the background of decreased blood coagulability.
Specific hematological phenomena
Laboratory diagnostics rely on unique features of the blood and bone marrow:
- Leukemic "hiatus" (hiatus leukaemicus): characteristic of acute myeloid leukemia. Blast cells and mature cells are present in the blood, but intermediate maturing forms are completely absent.
- Eosinophil-basophil "association": a specific sign of chronic myeloid leukemia, expressed as a simultaneous surge in the number of tumor eosinophils and basophils.
According to the leukocyte and blast count, the following forms are distinguished:
- Leukemic: leukocytes >30–50×10⁹/L, many blasts.
- Subleukemic: leukocytes above normal (up to 30–50×10⁹/L), many blasts.
- Leukopenic: leukocyte level is lowered, few blasts.
- Aleukemic: leukocytes are normal, blasts are absent in the blood (found only in hematopoietic organs).
Difference between leukemias and leukemoid reactions
It is extremely important to differentiate neoplastic processes from reactive changes:
- Nature: leukemias are caused by carcinogens and represent a primary lesion; leukemoid reactions are triggered by non-carcinogenic factors (infections, toxins) and are secondary in nature.
- Cells: in leukemias, blast forms are detected (except for the aleukemic form), whereas in reactions, normal young or maturing elements enter the blood.
- Degeneration: signs of degeneration are uncharacteristic for cells in leukemias, whereas in reactions (e.g., against the background of endotoxemia), they are clearly pronounced.
Briefly: answers to topical questions
What specific morphological and cytochemical signs of cellular atypia are characteristic of tumor cells in leukemia?
Tumor atypia in leukemias manifests in terms of sources through changes in cellular composition, hematological phenomena, and cytochemical disorders.
Morphological and hematological signs:
- Presence of leukemic blast cells; exception — the aleukemic form, in which blasts are absent in the peripheral blood.
- Leukemic hiatus (hiatus leukemicus) — the presence of blast and mature cell forms with the complete absence of transitional maturing forms; characteristic of acute myeloid leukemia.
- Eosinophil-basophil association — a significant simultaneous increase in tumor eosinophils and basophils; characteristic only of chronic myeloid leukemia.
- In the bone marrow: simultaneous coexistence of normal and tumor hematopoiesis, "rejuvenation" of the cellular composition, increase in the number of atypical hemoblastosis cells, large number of blast and immature tumor cells.
- In the classical hypergranular variant of acute promyelocytic leukemia: significant nuclear polymorphism, coarse purple-brown granulation densely filling the cytoplasm, large number of Auer rods.
Cytochemical signs:
- Changes in enzyme activity in cells, including acid phosphatase and myeloperoxidase.
- In acute promyelocytic leukemia — a very pronounced reaction to myeloperoxidase, lipids upon staining with Sudan Black B, and chloroacetate esterase.
What is the exact mechanism of development of resistance and tumor "escape" from cytostatic therapy in leukemias?
The development of resistance to therapy in leukemias is explained by the phenomenon of tumor progression associated with the genome instability of hemoblastosis cells.
The mechanism includes:
- the appearance of new mutant subclones within the initial clone;
- natural selection within the tumor: during the life cycle, the most adaptable subclones survive;
- transformation of clonality — transition from monoclonal tumors to polyclonal ones.
This mechanism explains the escape from the action of cytostatics, the development of resistance to therapy, the progressive course of hemoblastoses, and the generalization of the process.
What stages (monoclonal, polyclonal) are distinguished in the pathogenesis of tumor progression in leukemia?
In the tumor progression of hemoblastoses, clonality transformation is described: the transition from a monoclonal tumor to a polyclonal one.
- Monoclonal stage — presence of the initial clone of tumor cells.
- Polyclonal stage — appearance of new mutant subclones within the initial clone and their selection within the tumor.
An example of the polyclonal stage is blast crisis, in which blasts constitute more than 20% in the bone marrow and blood.
Acute hiatus, chronic association: in acute leukemia — a "hiatus" (hiatus) without intermediate forms; in chronic myeloid leukemia — an "association" of eosinophils and basophils.
Class and exam questions
What is a leukemic hiatus and for which pathology is it characteristic?
This is a phenomenon of the complete absence of transitional maturing forms between blasts and mature leukocytes in the peripheral blood. It is pathognomonic for acute myeloid leukemia.
What is the main difference between leukemias and leukemoid reactions?
Leukemias are a primary neoplastic disease caused by carcinogens with the appearance of blast cells. Leukemoid reactions are secondary, caused by non-carcinogenic factors, and are characterized by the release of normal young elements into the blood.
What causes anemia and thrombocytopenia in leukemias?
These syndromes develop due to massive expansion of neoplastic hematopoietic cells in the bone marrow, which mechanically crowd out the erythroid and megakaryoblast lineages.
What else to study on this topic
- Mechanisms of tumor progression and the role of telomerase activation
- Enzymatic disorders and metabolic atypia in leukemias
- Protein disorders: para- and dysproteinemias in multiple myeloma
- Pathogenesis of proliferative and cytopenic leukemoid reactions
- The role of reduced activity of antitumor defense mechanisms
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