Acute lymphoblastic leukemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Overview

Pathophysiology

The cause of most ALL is not known. In general, cancer is caused by damage to DNA that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth, or interrupting chemical signals that control growth. This damage may be caused by environmental factors such as chemicals, drugs or radiation.

In leukemias, including ALL, chromosomal translocations occur regularly. It is thought that most translocations occur before birth during fetal development. These translocations may trigger oncogenes to "turn on", causing unregulated mitosis where cells divide too quickly and abnormally, resulting in leukemia.

Some families have a hereditary predisposition to ALL.[1]

ALL is associated with exposure to radiation and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl nuclear reactor and atom bombs in Hiroshima and Nagasaki. In animals, exposure to benzene and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Patients who are treated for other cancers with radiation and chemotherapy often develop leukemias as a result of that treatment.

Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (metastasizing) to other organs.

Genetics

Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, has been increasingly recognized as an important predictor of outcome in ALL.[2]

Cytogenetic change Risk category
Philadelphia chromosome Poor prognosis
t(4;11)(q21;q23) Poor prognosis
t(8;14)(q24.1;q32) Poor prognosis
Complex karyotype (more than four abnormalities) Poor prognosis
Low hypodiploidy or near triploidy Poor prognosis
High hypodiploidy Good prognosis
del(9p) Good prognosis


References

  1. New Engl J Med somewhere
  2. Moorman A, Harrison C, Buck G, Richards S, Secker-Walker L, Martineau M, Vance G, Cherry A, Higgins R, Fielding A, Foroni L, Paietta E, Tallman M, Litzow M, Wiernik P, Rowe J, Goldstone A, Dewald G (2007). "Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial". Blood. 109 (8): 3189–97. PMID 17170120.

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