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Overview of Leukemia

By Jerry L. Spivak, MD, Professor of Medicine and Oncology and Director, Center for the Chronic Myeloproliferative Disorders, Johns Hopkins University School of Medicine

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The leukemias are cancers of the WBCs involving bone marrow, circulating WBCs, and organs such as the spleen and lymph nodes.


Risk of developing leukemia is increased in patients with

  • History of exposure to ionizing radiation (eg, post–atom bomb in Nagasaki and Hiroshima) or to chemicals (eg, benzene)

  • Prior treatment with certain antineoplastic drugs, particularly procarbazine, nitrosureas (cyclophosphamide, melphalan), and epipodophyllotoxins (etoposide, teniposide)

  • Infection with a virus (eg, human T-lymphotropic virus 1 and 2, Epstein-Barr virus)

  • Chromosomal translocations

  • Preexisting conditions, including immunodeficiency disorders, chronic myeloproliferative disorders, and chromosomal disorders (eg, Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, Down syndrome, infantile X-linked agammaglobulinemia)


Malignant transformation usually occurs at the pluripotent stem cell level, although it sometimes involves a committed stem cell with more limited capacity for self-renewal. Abnormal proliferation, clonal expansion, and diminished apoptosis (programmed cell death) lead to replacement of normal blood elements with malignant cells.

French-American-British (FAB) Classification of Acute Leukemias

FAB Classification


Acute lymphocytic leukemia


Lymphoblasts with uniform, round nuclei and scant cytoplasm


More variability of lymphoblasts

Sometimes irregular nuclei with more cytoplasm than L1


Lymphoblasts with finer nuclear chromatin and blue to deep blue cytoplasm that contains vacuoles

Acute myelogenous leukemia


Undifferentiated myeloblastic

No cytoplasmic granulation


Differentiated myeloblastic

Sparse granulation in few to many cells



Granulation typical of promyelocytic morphology



Mixed myeloblastic and monocytoid morphology



Pure monoblastic morphology



Predominantly immature erythroblastic morphology, sometimes megaloblastic appearance



Cells with shaggy borders that may show some budding

Manifestations of leukemia are due to

  • Suppression of normal blood cell formation

  • Organ infiltration by leukemic cells

Inhibitory factors produced by leukemic cells and replacement of marrow space may suppress normal hematopoiesis, with ensuing anemia, thrombocytopenia, and granulocytopenia.

Organ infiltration results in enlargement of the liver, spleen, and lymph nodes and, occasionally, in kidney and gonadal involvement. Meningeal infiltration results in clinical features associated with increasing intracranial pressure (eg, cranial nerve palsies).

Findings at Diagnosis in the Most Common Leukemias


Peak age of incidence


Any age

Middle and old age

Young adulthood

WBC count

High in 50%

Normal or low in 50%

High in 60%

Normal or low in 40%

High in 98%

Normal or low in 2%

High in 100%

Differential WBC count

Many lymphoblasts

Many myeloblasts

Small lymphocytes

Entire myeloid series


Severe in >90%

Severe in >90%

Mild in about 50%

Mild in 80%


Low in > 80%

Low in > 90%

Low in 20 to 30%

High in 60%

Low in 10%







In 60%

In 50%

Usual and moderate

Usual and severe

Other features

Without prophylaxis, CNS commonly involved

CNS rarely involved

Sometimes Auer rods in myeloblasts

Occasionally hemolytic anemia and hypogammaglobulinemia

Low leukocyte alkaline phosphatase level

Philadelphia chromosome–positive in > 90%


Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular phenotype and degree of differentiation on initial presentation.

Acute leukemias

Acute leukemias consist of predominantly immature, poorly differentiated cells (usually blast forms). Acute leukemias are divided into acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), which may be further subdivided by the French-American-British (FAB) classification (see Table: French-American-British (FAB) Classification of Acute Leukemias).

Chronic leukemias

Chronic leukemias have more mature cells than do acute leukemias. They usually manifest as abnormal leukocytosis with or without cytopenia in an otherwise asymptomatic person. Findings and management differ significantly between chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML).

Myelodysplastic syndromes

Myelodysplastic syndromes involve progressive bone marrow failure but with an insufficient proportion of blast cells (< 30%) for making a definite diagnosis of AML; 40 to 60% of cases evolve into AML.

Leukemoid reaction

A leukemoid reaction is marked granulocytic leukocytosis (ie, WBC > 50,000/μL) produced by normal bone marrow in response to systemic infection or cancer. Although not a neoplastic disorder, a leukemoid reaction with a very high WBC count may require testing to distinguish it from CML.

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