Mastering Medical
USMLE Step 2 CK · Hematology & Oncology

CLL vs CML

How to tell CLL and CML apart when a board question makes them look alike.

Step 2 CK pairs are in open beta while clinical review finishes. Spot an issue? Tell us.

Fastest separator

BCR-ABL positivity on molecular testing is the defining discriminator for CML.

Side by side

CLLCML
Key clue

Older patient with persistent absolute monoclonal B-cell lymphocytosis and smudge cells suggests chronic lymphocytic leukemia.

Marked leukocytosis with left-shifted myeloid precursors, basophilia, and BCR-ABL positivity suggests chronic myelogenous leukemia.

Mechanism

CLL is a clonal mature B-cell neoplasm with accumulation of apoptosis-resistant lymphocytes.

CML is a myeloproliferative neoplasm driven by constitutive BCR-ABL tyrosine kinase activity.

Labs and tests

CLL diagnosis requires clonal B-lymphocytes >=5000/uL for at least 3 months with flow cytometry showing CD5+, CD19+, CD23+ phenotype and often smudge cells.

CML shows high WBC often >25,000/uL with myelocyte bulge, absolute basophilia, low leukocyte alkaline phosphatase score, and Philadelphia chromosome t(9;22) with BCR-ABL PCR positivity.

The trap

A very high white count can be misread as CML in both diseases. The resolving clue is lineage and genetics: clonal CD5+ B-cell lymphocytosis supports CLL, while myeloid left shift with basophilia and BCR-ABL confirms CML.

The repair move

Next best step: confirm lineage and driver mutation before treatment decisions. Send peripheral blood flow cytometry when lymphoid disease is suspected, and send BCR-ABL PCR or FISH when myeloid left shift or basophilia is present. Start targeted therapy such as imatinib 400 mg orally daily for confirmed chronic-phase CML, while asymptomatic early CLL is commonly observed with close follow-up.

Try a free question

Core

A 64-year-old man has WBC 98,000/uL, splenomegaly, basophilia, and left-shifted myeloid cells on smear. What is the next best step in management?

Show answer and explanation

Answer: A. Order BCR-ABL molecular testing. When CML is suspected, confirming BCR-ABL is the key immediate step that directs targeted therapy.

Why the other choices are tempting

  • B. Rituximab targets B-cell disease and is not first-line empiric therapy for suspected CML.
  • C. No infection syndrome is described, and antibiotics do not address myeloproliferative disease.
  • D. Leukocytosis alone cannot distinguish CML from other leukemias.
  • E. Splenectomy is not first-line initial management for suspected CML.

Flashcards

Tap a card to flip it.

Which molecular finding immediately identifies chronic myelogenous leukemia?

Detection of BCR-ABL from the Philadelphia chromosome identifies CML.

What flow cytometry pattern supports chronic lymphocytic leukemia?

Clonal B cells coexpressing CD5, CD19, and CD23 support CLL.

Quick answers

What is the fastest way to tell CLL from CML?

BCR-ABL positivity on molecular testing is the defining discriminator for CML.

What is the key clue for CLL?

Older patient with persistent absolute monoclonal B-cell lymphocytosis and smudge cells suggests chronic lymphocytic leukemia.

What is the key clue for CML?

Marked leukocytosis with left-shifted myeloid precursors, basophilia, and BCR-ABL positivity suggests chronic myelogenous leukemia.

What is the common trap with CLL vs CML?

A very high white count can be misread as CML in both diseases. The resolving clue is lineage and genetics: clonal CD5+ B-cell lymphocytosis supports CLL, while myeloid left shift with basophilia and BCR-ABL confirms CML.