Leukemias

Leukaemia

For medical students2 min readUpdated 2026-10-10

Leukemias are primary neoplastic diseases of the hematopoietic tissue caused by carcinogens. The pathology is accompanied by mutations of the hematopoietic cell genome, impaired DNA repair, and uncontrolled proliferation of blast forms.

Cause of developmentCarcinogenic factors and genome instability

Leukemic hiatusNo intermediate forms between blasts and mature cells

Form typesLeukemic, subleukemic, leukopenic, and aleukemic

Pathological syndromesAnemia, thrombocytopenia, and hemorrhagic syndrome

Causes and Mechanisms of Neoplastic Transformation

The development of hemoblastoses is based not on the inheritance of the disease itself, but on the transmission of genome instability in hematopoietic cells—a reduced resistance of chromosomes to mutagens. Key risk factors include:

Abnormalities in DNA repair gene expression: cells are less efficient at eliminating mutations, which enhances the effect of carcinogens.
Iatrogenic exposures: the use of cytostatics and immunosuppressants significantly increases the risk of acute leukemias.
Ionizing radiation: radiation therapy and exposure with a latency period of 5–10 years.
Smoking: increases the likelihood of acute myeloid leukemia by 1.3–2 times.
Chronic antigenic stimulation: excessive load on the immune surveillance system predisposes to lymphoid neoplasms.

Tumor Progression and Signs of Atypia

Genome instability triggers a cascade of changes, including apoptosis evasion, telomerase activation, and oncogene expression. Mutant subclones emerge, among which the most adapted survive during intratumoral selection.

This explains the progressive course of the disease, the generalization of the process, and tumor evasion from cytostatic therapy.

In the bone marrow, normal and neoplastic hematopoietic lineages coexist, alongside a cellular "rejuvenation." In the peripheral blood, severe syndromes develop due to the expansion of tumor cells:

Anemia due to the displacement of erythropoiesis.
Thrombocytopenia resulting from the suppression of the megakaryoblastic lineage.
Hemorrhagic syndrome against the background of reduced blood clotting.

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, manifested by a simultaneous spike in the number of tumor eosinophils and basophils.

Depending on the leukocyte and blast counts, 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 decreased, few blasts.
Aleukemic: leukocytes are normal, blasts are absent from the blood (found only in hematopoietic organs).

Distinction Between Leukemias and Leukemoid Reactions

It is crucial to differentiate neoplastic processes from reactive changes:

Nature: leukemias are caused by carcinogens and are a primary lesion; leukemoid reactions are triggered by non-carcinogenic factors (infections, toxins) and are secondary in nature.
Cells: blast forms are found in leukemias (except for the aleukemic form), whereas normal young or maturing elements enter the blood in reactions.
Degeneration: signs of degeneration are not characteristic of cells in leukemias, whereas they are clearly expressed in reactions (e.g., against the background of endotoxemia).

Mnemonic

Acute hiatus, chronic association: in acute leukemia — a "hiatus" without intermediate forms; in chronic myeloid leukemia — an "association" of eosinophils and basophils.

Frequently asked questions

What specific morphological and cytochemical signs of cellular atypia characterize tumor cells in leukemia?

Tumor atypia in leukemias manifests as changes in cellular composition, hematological phenomena, and cytochemical disorders.

Morphological and hematological signs:

Presence of blast leukemic cells; exception — the aleukemic form, in which blasts are absent in the peripheral blood.
Leukemic hiatus (hiatus leukemicus) — presence of blast and mature cell forms with a complete absence of intermediate 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, an increase in the number of atypical hemoblastosis cells, and a large number of blast and immature tumor cells.
In the classic hypergranular variant of acute promyelocytic leukemia: significant nuclear polymorphism, coarse purple-brown granularity densely filling the cytoplasm, and a large number of Auer rods.

Cytochemical signs:

Altered enzyme activity in cells, including acid phosphatase and myeloperoxidase.
In acute promyelocytic leukemia — a very pronounced reaction to myeloperoxidase, lipids when stained with Sudan Black B, and chloroacetate esterase.

What is the exact mechanism of resistance development and tumor "evasion" from cytostatic therapy in leukemias?

The development of therapy resistance 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: the most adaptable subclones survive during vital activity;
clonal evolution — transition from monoclonal tumors to polyclonal ones.

This mechanism explains the evasion of cytostatics, the development of therapy resistance, 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?

Clonal evolution is described in the tumor progression of hemoblastoses: 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 account for more than 20% in the bone marrow and blood.

What is a leukemic hiatus and what pathology is it characteristic of?

This is a phenomenon where intermediate maturing forms between blasts and mature leukocytes are completely absent 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 characterized by the release of normal young elements into the blood.

What causes anemia and thrombocytopenia in leukemias?

These syndromes develop due to the massive expansion of neoplastic hematopoietic cells in the bone marrow, which mechanically displace the erythrocytic and megakaryoblastic lineages.

Go deeper

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