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USMLE Step 1Haematology and oncologyEP 13 of 14

AML vs ALL vs CML vs CLL: leukemia classification made simple

Sort the four main leukemias by lineage, maturity and age, and learn why a high white cell count can be the milder disease and a low one the emergency.

  • 5:44 video
  • 3 min read
  • 18 sources
  • Published 15 Nov 2026
Video lesson · 5:44 · Watch on YouTubeSeries: Hematology: Anemia, Coagulation & Oncology Basics · @medservatory
Chapters (13)
By the end of this lesson

Classify AML, ALL, CML and CLL by lineage (myeloid or lymphoid), maturity (acute blasts or chronic mature cells) and typical age group, and link each to its hallmark laboratory or genetic finding.

The short version

  1. Leukemias sort by lineage (myeloid or lymphoid) and by maturity (acute blasts or chronic mature cells).
  2. By the usual exam convention, 20 percent or more blasts in marrow or blood means acute leukemia.
  3. AML: Auer rods and myeloperoxidase-positive blasts. ALL: myeloperoxidase-negative, TdT-positive blasts, mostly in children.
  4. CML: the Philadelphia chromosome, t(9;22), fusing BCR to ABL, blocked by imatinib. CLL: smudge cells and CD5 with CD19, CD20 and CD23.
  5. The count alone does not tell you the severity; the maturity of the cells does.

AML vs ALL vs CML vs CLL: why the higher count is the milder disease

A 76-year-old man has a white cell count of 45 thousand and feels perfectly well. A 9-year-old girl's count is only 3 thousand, and she is pale, bruised and exhausted. The higher count belongs to the milder disease. How can that be?

The answer is that the number of cells matters less than how mature they are. This lesson sorts AML vs ALL vs CML vs CLL by lineage, maturity and age, so that each leukemia can be tied to its hallmark finding.

Spoiler for the two patients: the man's cells are mature, and the girl's marrow is full of blasts.[2][3][12][15]

Leukemia classification: lineage and maturity

Every blood cell descends from one hematopoietic stem cell in the marrow. It splits into a myeloid line, making granulocytes, monocytes, red cells and platelets, and a lymphoid line, making B, T and natural killer cells. Along each line, cells mature in steps, from blast to working cell.[1]

Leukemias are sorted by line and by maturity. Lineage is shown by myeloperoxidase, immunophenotype and Auer rods. Maturity separates acute leukemia (blasts) from chronic leukemia (mature cells).[2][4]

In acute leukemia, blasts crowd out the marrow, so red cells, platelets and normal white cells fall: pallor, bruising and infection.[2][3]

In chronic leukemia the cells are mature, so the marrow keeps making normal cells, and many patients are found by chance on a routine count.[12][15]

The four main leukemias at a glance
LeukemiaLineage and maturityTypical ageHallmark
AMLMyeloid, acute (myeloblasts)Mostly older adults; median about 68Auer rods; myeloperoxidase-positive blasts
ALLLymphoid, acute (lymphoblasts)Mostly children; peak 2–5 yearsMyeloperoxidase-negative, TdT-positive blasts
CMLMyeloid, chronicAdultsPhiladelphia chromosome, t(9;22), BCR–ABL
CLLLymphoid, chronic (small mature B cells)Median about 70CD5 with CD19, CD20, CD23; smudge cells

AML: myeloblasts, Auer rods and the APL subtype

Acute myeloid leukemia (AML) is a disease of myeloblasts, mostly in older adults, with a median age at diagnosis of about 68.[5][8]

The clue is the Auer rod, a needle-shaped inclusion in the cytoplasm. The blasts also stain positive for myeloperoxidase.[2][4]

The subtype to know is acute promyelocytic leukemia (APL): the t(15;17) translocation, the PML–RARA fusion, bleeding, and treatment with all-trans retinoic acid.[9][10]

ALL: lymphoblasts, TdT and young children

Acute lymphoblastic leukemia (ALL) is a disease of lymphoblasts, mostly in children, with incidence peaking between 2 and 5 years.[3][11]

Its blasts are myeloperoxidase negative and positive for TdT (terminal deoxynucleotidyl transferase).[4]

A frequent childhood subtype carries the t(12;21) translocation, ETV6–RUNX1, with an excellent outlook.[11]

CML: the Philadelphia chromosome and imatinib

Chronic myeloid leukemia (CML) occurs in adults. The blood shows a very high count of granulocytes at every stage of maturation, including basophils.[12][13]

The hallmark is the Philadelphia chromosome, the t(9;22) translocation fusing BCR to ABL. The fusion makes a tyrosine kinase that is always on, and imatinib blocks it.[12][14]

CLL: small mature B cells, CD5 and smudge cells

Chronic lymphocytic leukemia (CLL) is a disease of small, mature B cells, with a median age at diagnosis of about 70.[15][17]

The cells co-express CD5 with CD19, CD20 and CD23, and on the smear they break into smudge cells.[15][18]

Worked example: classify a case in two steps

A 58-year-old has a count of 160 thousand, granulocytes at every stage with basophils, and blasts under 5 percent.

Classify it
  1. Blasts under 5 percent and cells are mature, so chronic
  2. Granulocytes at every stage, so the granulocyte line: myeloid
  3. Chronic and myeloid is CML
  4. Look for BCR–ABL

Remember the rule that closes the lesson: the count alone does not tell you the severity; the maturity of the cells does.[2][12]

Practice question

Original · USMLE style
Your turnQB-MS-S1-HEME-007-01

A 4-year-old boy is brought to the physician because of 2 weeks of fatigue, bone pain and easy bruising. He is pale and has petechiae on both legs, enlarged cervical lymph nodes, and a palpable liver and spleen. Laboratory studies show:

Results
Hemoglobin7.1 g/dL
Leukocyte count62,000/mm³
Platelet count24,000/mm³
Peripheral blood smear80% blasts with scant, agranular cytoplasm
Cytochemical stain for myeloperoxidaseNegative
Which of the following findings is most likely to be present in this patient's leukemia?
Pick one option. Your answers stay on this device.

Common questions

What is the difference between acute and chronic leukemia?

Acute leukemia has 20 percent or more blasts in marrow or blood by the usual exam convention, and the blasts crowd out the marrow. In chronic leukemia the cells are mature, so the marrow keeps making normal cells.

How do you tell AML from ALL?

AML blasts are myeloperoxidase positive and may show Auer rods, mostly in older adults. ALL blasts are myeloperoxidase negative and TdT positive, mostly in children.

Which leukemia has the Philadelphia chromosome?

CML. The t(9;22) translocation fuses BCR to ABL and makes a tyrosine kinase that is always on, which imatinib blocks.

What are smudge cells?

Smudge cells are the form that CLL cells take on the smear, where they break apart. CLL cells are small, mature B cells that co-express CD5 with CD19, CD20 and CD23.

Transcript

Read the full narration, by chapter632 words

0:00A high count and a low count: which is worse?

A 76-year-old man has a white cell count of 45,000, and he feels perfectly well. A 9-year-old girl's count is only 3,000, and she is pale, bruised and exhausted. The higher count is the milder disease. How can that be? Today: sort the four main leukaemias by lineage, maturity and age.

0:22One stem cell, two lines: myeloid and lymphoid

Every blood cell descends from one haematopoietic stem cell in the marrow. It splits into a myeloid line, making granulocytes, monocytes, red cells and platelets, and a lymphoid line, making B, T and natural killer cells. Along each line, cells mature in steps, from blast to working cell. Leukaemias sort by line and maturity.

0:43Acute or chronic: the 20 percent blast rule

By the usual exam convention, 20% or more blasts in marrow or blood means acute leukaemia.

0:54Why acute disease fails the marrow and chronic is found by chance

In acute leukaemia, blasts crowd out the marrow, so red cells, platelets and normal white cells fall: pallor, bruising and infection. In chronic leukaemia the cells are mature, so the marrow keeps making normal cells and many patients are found by chance on a routine count. That is the puzzle solved: the man's cells are mature, and the girl's marrow is full of blasts.

1:20AML: myeloblasts, Auer rods, myeloperoxidase and the APL subtype

Acute myeloid leukaemia, AML: myeloblasts, mostly older adults, median age about 68. The clue is the Auer rod, a needle-shaped inclusion in the cytoplasm, and the blasts stain positive for myeloperoxidase. The subtype to know is acute promyelocytic leukaemia: the t(15;17) translocation, the PMLRAR alpha fusion, bleeding, and treatment with all-trans retinoic acid. Acute lymphoblastic

1:52ALL: lymphoblasts, TdT and young children

leukaemia, ALL: lymphoblasts, mostly children, peaking between two and five years. Its blasts are myeloperoxidase negative and positive for TdT, terminal deoxynucleotidyl transferase. A frequent childhood subtype has the t(12;21) translocation, ETV six RUNX one, with an excellent outlook.

2:19CML: the Philadelphia chromosome and imatinib

Chronic myeloid leukaemia, CML: adults, with a very high count of granulocytes at every stage of maturation, including basophils. The hallmark is the Philadelphia chromosome, the t(9;22) translocation fusing BCR to ABL. The fusion makes a tyrosine kinase that is always on, and imatinib blocks it. Chronic lymphocytic

2:44CLL: small mature B cells, smudge cells and CD5

leukaemia, CLL: small, mature B cells, median age about 70. They co-express CD5 with CD19, CD20 and CD23, and on the smear they break into smudge cells. Try one.

3:01Worked example: classify a case

A 58-year-old has a count of 160,000, granulocytes at every stage with basophils, and blasts under 5%. Mature, so chronic; granulocyte line, so myeloid. That is CML, and we would look for BCRABL. Your turn.

3:23Practice question

A 4-year-old boy has two weeks of fatigue, bone pain and easy bruising. He is pale, with petechiae, enlarged cervical nodes, and a palpable liver and spleen. Haemoglobin is 7.1 g/dL, white cell count 62,000 per cubic millimetre, platelets 24,000. The smear shows 80% blasts with scant, agranular cytoplasm, and a myeloperoxidase stain is negative. Which finding is most likely in this patient's leukaemia? A, Auer rods in the cytoplasm. B, terminal deoxynucleotidyl transferase positivity. C, the t(15;17) translocation. D, smudge cells with CD5 positive B cells. E, granulocytes at all stages, with basophilia. Pause here and decide. A is out: Auer rods mark myeloid blasts,

4:23Answer and explanation

which stain for myeloperoxidase. C is out: the t(15;17) translocation is acute promyelocytic leukaemia, a myeloid disease. D is out: smudge cells with CD5 positive B cells are CLL, a chronic disease of older adults. E is out: granulocytes at every stage with basophilia is CML, a chronic disease with few blasts. So the answer is B. A child with marrow failure and a negative myeloperoxidase has acute lymphoblastic leukaemia, and lymphoblasts express TdT. Three things to keep.

5:06Recap: three things to keep

One: acute means 20% or more blasts; chronic means mature cells. Two: AML, Auer rods; ALL, TdT in children; CML, Philadelphia chromosome; CLL, smudge cells with CD5. Three: the count alone does not tell you the severity; the maturity of the cells does.

5:33Next: oncogenes vs tumour suppressor genes

Next, oncogenes and tumour suppressor genes, and why a fusion like BCRABL drives cancer.

Sources

Numbers in the text, e.g. [1], point here
  1. Production of the Formed Elements. OpenStax Anatomy and Physiology 2e, section 18.2. openstax.org/books/anatomy-and-physiology-2e/pages/18-2-production-of-the-formed-elements
  2. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016. europepmc.org/article/PMC/PMC5030376
  3. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017. europepmc.org/article/PMC/PMC5520400
  4. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014. europepmc.org/article/PMC/PMC4235437
  5. Acute myeloid leukemia: 2025 update on diagnosis, risk-stratification and management. Am J Hematol. 2025. europepmc.org/article/PMC/PMC11966364
  6. 5th edition WHO classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022. europepmc.org/article/PMC/PMC9252913
  7. Acute myeloid leukemia: a concise review. 2016. europepmc.org/article/PMC/PMC4810104
  8. Treatment of Acute Myeloid Leukemia in the Elderly. 2026. europepmc.org/article/PMC/PMC13704431
  9. The coagulopathy of acute promyelocytic leukemia: an updated review. Cancers. 2023. europepmc.org/article/PMC/PMC10340352
  10. Acute promyelocytic leukemia (APL): a review of the literature. 2020. europepmc.org/article/PMC/PMC7082115
  11. Advances in the diagnosis and treatment of paediatric acute lymphoblastic leukemia. 2021. europepmc.org/article/PMC/PMC8124693
  12. Chronic myeloid leukemia: literature review. World J Clin Oncol. 2021. europepmc.org/article/PMC/PMC7918527
  13. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. europepmc.org/article/PMC/PMC7214240
  14. Imatinib in chronic myeloid leukemia: an overview. europepmc.org/article/PMC/PMC3894842
  15. Chronic lymphocytic leukemia: 2025 update on the epidemiology, pathogenesis, diagnosis and therapy. europepmc.org/article/PMC/PMC11803567
  16. Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies. 2020. europepmc.org/article/PMC/PMC7556519
  17. EHA Guidelines on management of chronic lymphocytic leukemia and Richter transformation. 2026. europepmc.org/article/PMC/PMC13254007
  18. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: an ERIC consensus. 2018. europepmc.org/article/PMC/PMC5817234

The 20 percent blast rule is the usual exam convention; WHO 5th edition and ICC relax it for some genetically defined AML. Hook and worked-example patients and all counts are invented teaching examples.

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (cropped, recoloured, outlined; blast versions recoloured red): haematopoietic stem cell, myeloid and lymphoid progenitors, neutrophil, basophil, monocyte, lymphocytes, erythrocyte, platelet, and the older man, girl and boy figures. The chromosome pairs, Auer rod, smudge cells, 2 x 2 grid, 20 percent bar, marrow, blood tube, question card, pocket card and all handwriting are drawn in code (original). No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-HEME-007.

For exam study only, not medical advice. Read the medical disclaimer.

In this series

Playlist on YouTube
← Previous · EP 12DIC vs TTP vs HUS: mechanism and the PT/PTT
  1. EP 01Microcytic anaemia: four causes, four iron fingerprints5:37
  2. EP 02Hepcidin: why iron falls in inflammation5:34
  3. EP 03B12 vs folate deficiency: MMA, homocysteine and the nerves5:23
  4. EP 04Intravascular vs extravascular haemolysis: site and labs5:27
  5. EP 05G6PD deficiency vs hereditary spherocytosis, by mechanism5:36
  6. EP 06Sickle cell disease pathophysiology: HbS to vaso-occlusion5:26
  7. EP 07Primary haemostasis: platelet adhesion, activation and aggregation5:53
  8. EP 08Coagulation cascade: PT vs aPTT, pathway by pathway5:21
  9. EP 09Von Willebrand disease vs haemophilia: the labs that separate them5:32
  10. EP 10Anticoagulants: target, monitoring test and reversal agent5:34
  11. EP 11Heparin-induced thrombocytopenia: why a low count clots5:29
  12. EP 12DIC vs TTP vs HUS: mechanism and the PT/PTT5:33
  13. EP 13AML vs ALL vs CML vs CLL: leukemia classification made simple5:44
  14. EP 14Oncogenes vs tumour suppressor genes: one hit or two5:17