Leukemia: Understanding Blood Cancer Types, Causes, and Treatment

Leukemia is a malignancy of hematopoietic (blood-forming) cells in the bone marrow, characterized by uncontrolled proliferation of abnormal white blood cells that crowd out normal hematopoiesis.

Classification (By Speed and Lineage)

	Acute (Rapid)	Chronic (Slow)
Lymphoid	ALL (common in children)	CLL (common in older adults)
Myeloid	AML (adults)	CML (adults; BCR-ABL1)

Pathogenesis

• Genetic mutations (translocations, point mutations, deletions) in hematopoietic stem/progenitor cells.
• Blocked differentiation → accumulation of immature "blasts" (acute) or mature but dysfunctional cells (chronic).
• Normal blood cell production suppressed → anemia, thrombocytopenia, neutropenia.

Risk Factors

• Prior chemotherapy/radiation (therapy-related AML/MDS)
• Benzene, formaldehyde exposure
• Genetic syndromes (Down syndrome → ↑ALL/AML; Fanconi anemia)
• Family history (modest increase)
• Smoking (AML)
• HTLV-1 (ATLL)

Symptoms

• Fatigue, pallor (anemia)
• Recurrent infections (neutropenia)
• Bruising, bleeding (thrombocytopenia)
• Fever, night sweats, weight loss
• Lymphadenopathy, splenomegaly (lymphoid)
• Bone pain (ALL in children)

Diagnosis

• CBC with differential → blasts, cytopenias
• Bone marrow aspirate/biopsy: morphology, flow cytometry, cytogenetics (karyotype, FISH), molecular (NGS panel)
• Lumbar puncture (ALL, high-risk AML) for CNS involvement.

Treatment Overview

• Acute: Intensive induction chemotherapy → consolidation ± allogeneic transplant.
• CML: TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) → deep molecular response; normal lifespan achievable.
• CLL: BTK inhibitors (ibrutinib, acalabrutinib), BCL-2 (venetoclax), anti-CD20; chemoimmunotherapy declining.
• Supportive: Transfusions, growth factors, antimicrobials, TLS prophylaxis.

Prognosis varies widely by subtype, age, genetics, and fitness. Pediatric ALL >90% cure; AML in older adults remains challenging. Clinical trials are essential for continued advances.