Leukemia
Also known as: leukaemia
Leukemia is a malignancy of blood-forming cells in which abnormal white blood cell precursors proliferate in the bone marrow and spill into the bloodstream. Crowding of normal marrow produces anemia, infection risk, and bleeding.
In leukemia, a clone of hematopoietic cells acquires mutations that drive uncontrolled proliferation and block normal maturation. The expanding clone occupies marrow space needed for normal hematopoiesis, so patients typically present with the triad of anemia (fatigue, pallor), neutropenia (recurrent or severe infection), and thrombocytopenia (bruising, petechiae, mucosal bleeding). Leukemic cells also infiltrate the spleen, liver, and lymph nodes.
Classification runs along two axes: acute versus chronic, and lymphoid versus myeloid. Acute leukemias are dominated by immature blasts and progress rapidly; chronic leukemias involve more mature-appearing cells and follow an indolent course. This yields four principal entities. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, is associated with Down syndrome, and can involve the central nervous system and testes. Acute myeloid leukemia (AML) occurs mainly in adults and shows myeloperoxidase-positive blasts, with Auer rods as the classic smear finding. Chronic lymphocytic leukemia (CLL) affects older adults and shows fragile lymphocytes that rupture into smudge cells. Chronic myeloid leukemia (CML) is defined by the Philadelphia chromosome, the t(9;22) translocation producing the BCR-ABL fusion tyrosine kinase, and may progress to blast crisis.
Diagnosis rests on a complete blood count with differential, peripheral blood smear, bone marrow aspiration and biopsy, and flow cytometry to establish lineage, supported by cytogenetic and molecular studies that also guide prognosis. Distinguishing AML from CML on an exam usually turns on blast percentage and the presence of BCR-ABL rather than on white cell count alone.
USMLE Step 1 tests leukemia in detail within hematology and oncology, emphasizing smear findings, translocations, and age associations. The CCMA exam addresses it more practically through white blood cell analysis and interpretation of laboratory results, and the MCAT touches the underlying molecular biology through recombinant DNA and biotechnology.
Key takeaways
- Leukemia is a clonal malignancy of blood cell precursors that crowds out normal marrow, causing anemia, infection, and bleeding.
- Acute leukemias are blast-predominant and rapidly progressive; chronic leukemias involve more mature cells and progress slowly.
- ALL is the most common childhood cancer and is associated with Down syndrome; AML is mainly an adult disease with Auer rods on smear.
- CLL shows smudge cells in older adults, while CML is defined by the Philadelphia chromosome t(9;22) and the BCR-ABL fusion.
- Diagnosis uses CBC with differential, peripheral smear, bone marrow biopsy, flow cytometry, and cytogenetics.