What is leukemia?

What is Leukemia?

Leukemia is a clonal proliferation of hematopoietic stem cells in the bone marrow characterized by the accumulation of abnormal white blood cells that compromise normal bone marrow function, leading to cytopenias and potential organ infiltration. 1

Types of Leukemia

Leukemia is broadly classified into four main categories based on cell type and disease progression:

• Acute Myeloid Leukemia (AML): Characterized by rapid accumulation of immature myeloid cells (myeloblasts) in the bone marrow and blood, with ≥20% blasts required for diagnosis 2

• Chronic Myeloid Leukemia (CML): Distinguished by excessive production of mature and maturing granulocytes with the presence of Philadelphia chromosome t(9;22) and BCR-ABL fusion gene 2

• Acute Lymphoblastic Leukemia (ALL): Characterized by proliferation of immature lymphoid cells, more common in children, requiring >20% lymphoblasts for diagnosis 2

• Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Progressive accumulation of mature-appearing but functionally incompetent lymphocytes, primarily affecting older adults 2

Pathophysiology

• Leukemia results from genetic alterations in hematopoietic stem cells leading to uncontrolled proliferation and impaired differentiation 2

• Chromosomal abnormalities and gene mutations play crucial roles in leukemogenesis, with specific genetic markers associated with different leukemia subtypes 2

• The abnormal cells accumulate in bone marrow, peripheral blood, and can infiltrate other organs including spleen, liver, lymph nodes, and extramedullary sites 3

Clinical Manifestations

Symptoms result from two primary mechanisms:

• Bone marrow failure: Leading to:

  • Anemia (fatigue, weakness, pallor)
  • Thrombocytopenia (bruising, bleeding)
  • Neutropenia (recurrent infections) 1

• Leukemic infiltration: Causing:

  • Hepatosplenomegaly
  • Lymphadenopathy
  • Bone pain
  • Central nervous system involvement
  • Skin lesions (particularly in certain subtypes) 3

Diagnostic Approach

The diagnosis of leukemia requires:

• Complete blood count (CBC) with differential: Often showing leukocytosis, anemia, and/or thrombocytopenia 4

• Peripheral blood smear examination: Revealing abnormal cells, with morphology providing initial clues to leukemia type 4

• Bone marrow aspiration and biopsy: Essential for definitive diagnosis, showing increased cellularity and blast percentage 2, 4

• Immunophenotyping: Using flow cytometry to identify cell lineage and maturation stage 2, 4

• Cytogenetic analysis: Detecting chromosomal abnormalities critical for classification and prognosis 2, 4

• Molecular genetic testing: Identifying specific mutations and gene rearrangements 2, 4

Disease-Specific Features

Acute Myeloid Leukemia (AML)

• Characterized by ≥20% myeloblasts in bone marrow or peripheral blood 2
• Subtypes include AML with recurrent genetic abnormalities, AML with myelodysplasia-related changes, therapy-related AML, and AML not otherwise specified 2
• Myeloid sarcomas (extramedullary myeloid tumors) occur in 5-7% of AML cases 3

Chronic Myeloid Leukemia (CML)

• Distinguished by the presence of Philadelphia chromosome t(9;22) and BCR-ABL fusion gene 2
• Characterized by increased granulocytic proliferation with maintained differentiation 2
• Typically progresses through chronic, accelerated, and blast phases if untreated 2

Acute Lymphoblastic Leukemia (ALL)

• More common in children but can occur at any age 2, 5
• Classified as B-cell or T-cell based on immunophenotype 2
• Philadelphia chromosome-positive ALL represents a distinct entity with specific treatment approaches 5

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

• Most prevalent adult leukemia in Western countries 2
• Characterized by accumulation of small, mature-appearing lymphocytes 2
• CLL and SLL represent different manifestations of the same disease, differing primarily in the site of involvement 2

Prognosis and Outcomes

Prognosis varies significantly based on:

• Leukemia subtype
• Patient age and comorbidities
• Genetic and molecular characteristics
• Response to initial therapy 6

Five-year survival rates are highest in:

• Younger patients
• Patients with CML or CLL
• Those with favorable cytogenetic profiles 1

Without treatment, acute leukemias are rapidly fatal, with median survival of less than 3 months 7

Treatment Approaches

Treatment strategies depend on leukemia type, patient factors, and disease characteristics:

• Chemotherapy: Backbone of treatment for most leukemias 2, 5
• Targeted therapies: Including tyrosine kinase inhibitors for CML and Philadelphia-positive ALL 5
• Immunotherapy: Monoclonal antibodies and CAR T-cell therapy 5
• Hematopoietic stem cell transplantation: Potentially curative for high-risk leukemias 5, 6

Treatment complications include tumor lysis syndrome, infections from immunosuppression, and long-term effects in survivors 1