Acute Lymphoblastic Leukemia (ALL) – Simplified

What is Acute Lymphoblastic Leukemia (ALL)?

ALL (also called acute lymphoblastic lymphoma in some cases) is a neoplasm of immature B or T cells.

  • These immature cells are called lymphoblasts.

  • They may be B-lymphoblasts or T-lymphoblasts.

Who gets Acute Lymphoblastic Leukemia most commonly?

  • B-ALL: About 85% of cases, most common in children under 15 years. Peak incidence is below 3 years of age.

  • T-ALL: Presents in adolescents, usually as a thymic mass.

  • Boys are more commonly affected than girls.

  • ALL is the most common cancer of childhood.

What causes Acute Lymphoblastic Leukemia ? (Pathogenesis)

The disease arises because of genetic mutations that affect transcription factors needed for normal B- and T-cell development.

Two key mechanisms:

  1. Maturation arrest → cells cannot differentiate further.

  2. Increased proliferation/self-renewal → cells behave like stem cells.

Together, these changes produce immortal lymphoblast clones that crowd the bone marrow and suppress normal blood cell formation.

Acute Lymphoblastic Leukemia

Which genes are involved?

  • B-cell ALL: PAX5, TCF3, ETV6, RUNX1, BCR-ABL1 (Philadelphia chromosome), KMT2A, PBX1.

  • T-cell ALL: NOTCH1 gene mutation (critical for T-cell development).

Are single mutations enough to cause Acute Lymphoblastic Leukemia?

No. ALL is a multi-step process.

  • Initial mutations cause maturation arrest.

  • Additional driver mutations (like BCR-ABL1 fusion or RAS pathway mutations) push cells towards full leukemogenesis.

What about chromosomal abnormalities?

Seen in 90% of ALL cases.

  • Hyperdiploidy (>50 chromosomes): Good prognosis.

  • Hypodiploidy (<44 chromosomes): Poor prognosis.

  • Structural translocations:

    • ETV6-RUNX1 fusion

    • BCR-ABL1 fusion

    • TCF3-PBX1 fusion

These are important for diagnosis, risk stratification, and targeted therapy.

What happens in the bone marrow?

Accumulation of lymphoblasts → suppression of normal hematopoiesis →

  • Anemia (fatigue, pallor)

  • Neutropenia (fever, infections)

  • Thrombocytopenia (bleeding, petechiae)

Leukemic cells may also spread to blood, CNS, lymph nodes, liver, spleen, and testes.

What does Acute Lymphoblastic Leukemia look like morphologically?

  • Peripheral smear:

    • Anemia

    • Leukocytosis with blasts

    • Neutropenia

    • ThrombocytopeniaAcute Lymphoblastic Leukemia

  • Bone marrow:

    • Hypercellular marrow packed with lymphoblasts

    • Lymphoblasts: large cells, scant basophilic cytoplasm, delicate nuclear chromatin, small nucleoli, sometimes convoluted nuclei

  • Histopathology:

    • Classic “starry sky” pattern due to macrophages eating apoptotic cells

How do you differentiate ALL from AML?

  • Morphology may be tricky.

  • Special stain: Periodic Acid–Schiff (PAS) shows block positivity in lymphoblasts.

Acute Lymphoblastic Leukemia

  • Definitive diagnosis: Flow cytometry

    • B-ALL: CD19, CD22, CD10, TdT positive

    • T-ALL: CD1, CD2, CD5, CD7 positive

Click to read more about Cytochemical stains  in Hematolymphoid neoplasms

 

What are the clinical features of Acute Lymphoblastic Leukemia ?

  • Abrupt onset with stormy course

  • Marrow failure signs:

    • Fatigue (anemia)

    • Fever (neutropenia)

    • Bleeding (thrombocytopenia)

  • Bone pain (marrow expansion, periosteal infiltration)

  • Lymphadenopathy, hepatosplenomegaly, testicular enlargement

  • CNS involvement: headache, vomiting, nerve palsies (more common in ALL than AML)

How is Acute Lymphoblastic Leukemia treated?

  • Aggressive chemotherapy

    • 95% of children achieve remission

    • 75–85% are cured

  • This is why it is very important to distinguish ALL from AML, as AML is usually not curable with chemotherapy alone.

What are the prognostic factors in Acute Lymphoblastic Leukemia ?

Favorable prognosis:

  • Age 2–10 years

  • Low WBC count

  • Hyperdiploidy (>50 chromosomes)

  • Extra copies of chromosomes 4 and 10

  • Translocation t(12;21) → ETV6-RUNX1 fusion

Poor prognosis:

  • Age <2 years or adolescence/adulthood

  • CNS involvement

  • Very high WBC count (>100,000/µL)

  • Hypodiploidy

Can ALL benefit from targeted therapy?

Yes.

  • Patients with tyrosine kinase mutations (e.g., Philadelphia chromosome with BCR-ABL1) can receive targeted therapy (TKIs) along with chemotherapy

Click below to watch the  video on Acute Lymphoblastic Leukemia