Leukemia — Cancers of the Blood and Bone Marrow

Leukemia arises when mutations in haematopoietic stem cells or progenitor cells disrupt normal blood cell development. Under healthy conditions, the bone marrow generates balanced proportions of red blood cells, platelets, and white blood cells. In leukemia, acquiring genetic or epigenetic defects arrests cellular differentiation, trapping cells in an immature blast state or promoting unregulated accumulation of mature-appearing but functionally defective leukocytes.

These malignancies are categorised into four primary subtypes along two axes: speed of progression (acute versus chronic) and cell lineage (myeloid versus lymphoid). Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) advance rapidly, requiring immediate medical therapy. Chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) develop more indolently, often remaining asymptomatic during their early phases.

Because leukemia circulates throughout the vascular system, it does not form solid tumours and is considered systemic from onset. Early identification is vital, especially for acute leukemias, where symptoms can escalate quickly within days. Understanding the exact cytogenetic and molecular subtype of leukemia directly guides targeted interventions. Today, precision medicine allows oncologists to match specific genetic alterations with tailor-made therapies, converting once-fatal subtypes into manageable or curable conditions.

Initial assessment begins with a full blood count (FBC) and peripheral blood smear, revealing abnormal cell numbers and circulating blasts. Bone marrow aspiration and trephine biopsy provide definitive diagnostic tissue. Samples undergo flow cytometry for immunophenotyping, alongside cytogenetic karyotyping and molecular assays (such as PCR or next-generation sequencing) to detect abnormalities like the Philadelphia chromosome (BCR-ABL1), FLT3, NPM1, or TP53 mutations.

Leukemia encompasses several distinct clinical entities: Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Chronic Myeloid Leukemia (CML). Rarer variants include hairy cell leukemia, acute promyelocytic leukemia (APL), and prolymphocytic leukemia. It can also develop as a secondary therapy-related myeloid neoplasm following prior chemotherapy or radiation therapy.

Therapy varies dramatically across subtypes. Acute leukemias typically require intensive multi-agent induction chemotherapy, followed by consolidation or allogeneic haematopoietic stem cell transplantation. Chronic leukemias frequently respond to targeted oral therapies, such as tyrosine kinase inhibitors (e.g., imatinib) for CML, or Bruton tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) and BCL-2 antagonists (e.g., venetoclax) for CLL. Immunotherapies, including bispecific antibodies and CAR-T cell therapies, play prominent roles in relapsed ALL.