What is Leukemia?
Leukemia is a clonal proliferation of hematopoietic stem cells in the bone marrow that leads to the accumulation of abnormal white blood cells, resulting in compromise of normal bone marrow function and subsequent cytopenias. 1
Types of Leukemia
Leukemia is broadly classified into four major categories based on cell lineage (myeloid vs. lymphoid) and disease course (acute vs. chronic):
- Acute Myeloid Leukemia (AML): Characterized by rapid proliferation of immature myeloid cells (myeloblasts) with ≥20% blasts in bone marrow or peripheral blood 2
- Acute Lymphoblastic Leukemia (ALL): Characterized by proliferation of immature lymphoid cells (lymphoblasts), more common in children 2
- Chronic Myeloid Leukemia (CML): Characterized by excessive proliferation of relatively mature granulocytes with the Philadelphia chromosome t(9;22) translocation 2, 3
- Chronic Lymphocytic Leukemia (CLL): Characterized by accumulation of mature-appearing but functionally incompetent lymphocytes 2
Pathophysiology
Leukemia develops through:
- Genetic alterations leading to uncontrolled proliferation and impaired differentiation of hematopoietic stem cells 2
- Accumulation of these abnormal cells in bone marrow, peripheral blood, and sometimes other tissues 2
- Suppression of normal hematopoiesis resulting in anemia, neutropenia, and thrombocytopenia 1
Clinical Manifestations
Symptoms of leukemia result from:
- Bone marrow failure: Anemia (fatigue), neutropenia (infections), thrombocytopenia (bleeding, bruising) 1
- Leukemic infiltration: Organomegaly (spleen, liver), lymphadenopathy, bone pain 4
- Systemic symptoms: Fever, weight loss, night sweats 1
Diagnostic Approach
Diagnosis requires:
- Complete blood count (CBC): Often reveals leukocytosis and abnormalities in other cell lines 5
- Peripheral blood smear: May show leukemic blasts or abnormal cell morphology 5
- Bone marrow examination: Essential for definitive diagnosis, showing ≥20% blasts in acute leukemias 2, 5
- Immunophenotyping: Flow cytometry to determine cell lineage and confirm clonality 5
- Cytogenetic analysis: Mandatory for proper classification and risk stratification 5
- Molecular genetic testing: To identify specific mutations and gene rearrangements 5
Disease-Specific Features
Acute Myeloid Leukemia (AML)
- Requires ≥20% myeloblasts in bone marrow or blood 2
- Classified into subtypes based on morphology, cytogenetics, and molecular features 2
- Untreated AML is rapidly fatal with median survival <3 months 6
Chronic Myeloid Leukemia (CML)
- Characterized by the Philadelphia chromosome t(9;22) and BCR-ABL fusion gene 2
- Presents with leukocytosis, basophilia, and immature granulocytes in peripheral blood 2
- Often progresses through chronic, accelerated, and blast phases if untreated 3
Chronic Lymphocytic Leukemia (CLL)
- Most prevalent adult leukemia in Western countries 2
- Characterized by accumulation of small, mature-appearing lymphocytes 2
- Often indolent course with variable progression 2
Acute Lymphoblastic Leukemia (ALL)
- Most common childhood cancer but can occur in adults 7
- Characterized by proliferation of lymphoid progenitor cells 7
- Better outcomes in pediatric patients (80-90% survival) compared to adults (40-50%) 7
Prognosis
Prognosis varies widely depending on:
- Leukemia subtype 1
- Patient age (generally better in younger patients) 1
- Cytogenetic and molecular abnormalities 2
- Response to initial therapy 7
- Presence of comorbidities 3
Five-year survival rates are highest in younger patients and in those with chronic forms of leukemia (CML, CLL) 1.