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Leukemias

 
, medical expert
Last reviewed: 05.07.2025
 
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Leukemias are malignant tumors of the leukocyte lineage with involvement of the bone marrow, circulating leukocytes and organs such as the spleen and lymph nodes in the pathological process.

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Cause and pathophysiology of leukemia

Malignant transformation usually occurs at the level of pluripotent stem cells, although sometimes transformation occurs in committed stem cells with a more limited capacity for differentiation. Abnormal proliferation, clonal expansion, and inhibition of apoptosis (programmed cell death) lead to the replacement of normal blood cells by malignant cells.

The risk of developing most leukemias is increased by a history of exposure to ionizing radiation (eg, after the atomic bombings of Nagasaki and Hiroshima), chemicals (eg, benzene); treatment with certain anticancer drugs, including procarbazine, nitrosoureas (cyclophosphamide, melphalan), and epipodophyllotoxins (etoposide, teniposide); viral infections (eg, human T-lymphotropic virus types 1 and 2, Epstein-Barr virus); chromosomal translocations; and a number of diseases, such as immunodeficiency states, chronic myeloproliferative disorders, and chromosomal diseases (eg, Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, Down syndrome, infantile X-linked agammaglobulinemia).

Clinical manifestations of leukemia are caused by the suppression of the mechanisms of formation of normal cellular elements and infiltration of organs by leukemic cells. Leukemic cells produce inhibitors and replace normal cellular elements in the bone marrow, which leads to suppression of normal hematopoiesis with the development of anemia, thrombocytopenia and granulocytopenia. Infiltration of organs leads to enlargement of the liver, spleen, lymph nodes, and sometimes the kidneys and gonads are affected. Infiltration of the meninges leads to clinical manifestations that are caused by increased intracranial pressure (for example, paralysis of the cranial nerves).

Classification of leukemia

Originally, the terms acute and chronic leukemia referred to the life expectancy of patients, but leukemias are now classified by the degree of maturity of the cells. Acute leukemias consist predominantly of immature, poorly differentiated cells (usually blast forms); chronic leukemias are characterized by more mature cells. Acute leukemias are divided into lymphoblastic (ALL) and myeloblastic (AML) types, which are divided into subtypes according to the French-American-British (FAB) classification. Chronic leukemias are divided into lymphocytic (CLL) and myelocytic (CML).

Myelodysplastic syndromes include conditions with progressive bone marrow failure but with an insufficient proportion of blast cells (<30%) to clearly meet the diagnosis of acute myeloid leukemia; 40 to 60% of cases of myelodysplastic syndrome evolve into acute myeloid leukemia.

A leukemoid reaction is a marked granulocytic leukocytosis (i.e., a white blood cell count >30,000/μL) produced by normal bone marrow in response to a systemic infection or cancer. Although not a neoplastic disorder, a leukemoid reaction with very high leukocytosis may require differential diagnosis with chronic myelogenous leukemia.

French-American-British classification of acute leukemia (FAB classification)

Acute lymphoblastic leukemia

L1

Monomorphic lymphoblasts with round nuclei and a small volume of cytoplasm

L2

Polymorphic lymphoblasts with nuclei of various shapes and a larger volume of cytoplasm than in L1

L3

Lymphoblasts with small particles of chromatin in the nucleus and blue or dark blue cytoplasm with vacuolization

Acute myeloid leukemia

M1

Undifferentiated myeloid leukemia; no granules in the cytoplasm

M2

Myeloblastic leukemia with cell differentiation; scanty granulation may be recorded both in individual cells and in large numbers of them

MZ

Promyelocytic leukemia; granules are typical of promyelocytes

M4

Myelomonoblastic leukemia; mixed myeloblastic and monocytoid morphology

M5

Monoblastic leukemia, monoblastic morphology

Mb

Erythroleukemia; morphology predominantly immature erythroblasts, sometimes megaloblasts

M7

Megakaryoblastic leukemia; cells with processes, budding may be noted

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