Definition:
Chronic lymphoid leukemia (CLL) is a clonal malignancy of small, mature-appearing lymphocytes, almost always of B-cell origin. It is the most common leukemia in adults (especially those >65 years old).
CLL is considered part of a spectrum with small lymphocytic lymphoma (SLL) — they are morphologically and immunophenotypically identical, but differ in degree of blood involvement.
Etiology:
- Unknown primary cause
- Risk factors include:
- Genetic predisposition (family history of CLL)
- Monoclonal B-cell lymphocytosis (MBL) as a precursor lesion
- MBL = presence of <5 × 10⁹/L monoclonal B-cells without CLL features
- Can progress to full-blown CLL in some patients
- Ionizing radiation and chemical exposures are less clearly associated than in CML
Pathogenesis:
- Clonal expansion of functionally incompetent B-lymphocytes
- Accumulation due to:
- Decreased apoptosis (not rapid proliferation like in other leukemias)
- Bone marrow, lymph nodes, spleen infiltration
- Eventually causes:
- Marrow failure (↓ RBCs, platelets)
- Immune dysfunction (↓ immunoglobulin levels → recurrent infections)
- Autoimmune hemolytic anemia (AIHA) or thrombocytopenia in some cases
- Common genetic abnormalities:
- del(13q) (good prognosis)
- Trisomy 12 (intermediate prognosis)