Bit · Heme/Onc
AML vs ALL vs CML vs CLL
Four leukemias that split first by acute/chronic (blast burden) and then by lineage (lymphoid/myeloid). The pivot is age + smear finding.
Mechanism
The first split is on clinical tempo and blast count:
- Acute — >20% blasts in bone marrow, rapid progression, presents with marrow failure (cytopenias, infection, bleeding).
- Chronic — mature-looking malignant cells, indolent course, often found on routine CBC.
The second split is on lineage — lymphoid vs myeloid. Each combination has a signature:
- AML — adults. Auer rods (peroxidase-positive crystalline inclusions) are pathognomonic. Subtype M3 (acute promyelocytic, APL) has t(15;17) and risk of DIC; responds dramatically to all-trans retinoic acid.
- ALL — children (peaks age 2–5). TdT-positive blasts. t(12;21) good prognosis in kids; t(9;22) Philadelphia poor prognosis in adults. CNS involvement common.
- CML — middle-aged adults. Philadelphia chromosome t(9;22) → BCR-ABL fusion → constitutively active tyrosine kinase. Treated with imatinib. May transform to a blast crisis.
- CLL — older adults (>60). Mature B cells. Smudge cells on smear. Often asymptomatic on routine labs. May be associated with warm autoimmune hemolytic anaemia.
Differentiator Table
| AML | ALL | CML | CLL | |
| Acute or chronic | Acute | Acute | Chronic | Chronic |
| Lineage | Myeloid | Lymphoid (B or T) | Myeloid | Lymphoid (mature B) |
| Typical age | Adults (median ~65) | Children (peak 2–5) | Adults (40–60) | Older adults (>60) |
| Pathognomonic smear | Auer rods, myeloperoxidase + | TdT + blasts | Massive WBC with all maturation stages | Smudge cells, mature small lymphocytes |
| Genetic hallmark | t(15;17) APL (M3); t(8;21); inv(16) | t(12;21) — good in kids; t(9;22) — poor in adults | t(9;22) Philadelphia → BCR-ABL | Often del(13q), del(11q), trisomy 12 |
| Bone marrow | >20% myeloid blasts | >20% lymphoid blasts | Hypercellular, full spectrum of myeloid maturation | Mature lymphocyte infiltration |
| First-line treatment | Induction chemo (7+3); ATRA for APL | Multi-agent chemo + CNS prophylaxis | Imatinib (tyrosine kinase inhibitor) | Often watch-and-wait early; ibrutinib, BR, etc. |
The Pivot
Two questions:
- Acute or chronic? >20% blasts and marrow failure → acute. Indolent + mature cells → chronic.
- Smear finding? Auer rods → AML. TdT+ blasts → ALL. Massive WBC across maturation + Philadelphia → CML. Smudge cells in an older adult → CLL.
Always look for APL specifically — t(15;17), risk of DIC, treat with ATRA. It's the AML subtype NBME loves.
NBME-Style Stem
A 68-year-old man is found on routine CBC to have a WBC of 92,000/mm³, mostly mature-appearing lymphocytes. Peripheral smear shows numerous smudge cells. He is asymptomatic. Which of the following is the most likely diagnosis?
Concept Anchor
Acute leukemia is a blast invasion that crashes the marrow; chronic leukemia is a slow expansion of a more mature clone. The smear cell that's not supposed to be there (Auer rods, TdT+ blast, Philadelphia, smudge cell) tells you which one.