Diagnosis and tests

How a diagnosis is made

A leukemia diagnosis is not made in a single moment: it begins with a suspicion and becomes precise as the results of several tests come together. This topic calmly explains the order in which doctors think, which test answers which question and why the final diagnosis takes a little time.

Last updated: ~5 min read
Translucent glowing puzzle pieces — a drop of blood, a cell, a chromosome and a DNA helix — floating on a dark navy background and slowly joining into one complete glowing circle.
Figure 1.Concept: a diagnosis is built from several pieces.

01Short answer

Diagnosing leukemia usually goes through three stages. The first is suspicion: tiredness, frequent infections, bruising or a blood count that turns out abnormal, sometimes by chance. The second is confirmation: leukemia cells are found in a blood smear and especially in the bone marrow (blasts or, in chronic leukemia, mature but abnormal cells). The third is precise characterisation: flow cytometry shows the type of cell (myeloid, B or T lymphoid), and cytogenetic and molecular tests show changes in chromosomes and genes. Using systems such as the WHO (2022) and the International Consensus Classification, all of this becomes the final diagnosis and risk group. The treatment plan is built on that final picture. In chronic lymphocytic leukemia, the diagnosis is often made from blood counts and flow cytometry of the blood alone, and a bone marrow test is not always needed.

02Simple explanation

You can think of diagnosis as putting a puzzle together. The blood count is the first piece: it says “something is not right” but not exactly what.

Next, doctors look at a blood smear under the microscope. Immature cells (blasts) may be visible there, which strengthens the suspicion of leukemia.

For most types of leukemia, the main confirmation is a bone marrow test. Blood cells are made in the marrow, so that is where the disease starts.

The marrow sample is shared between several laboratories: one looks at the cells, one reads their “labels” (markers), one checks the chromosomes and one the genes. Together they give the leukemia its exact name.

This takes several days, sometimes a few weeks. That is normal: an accurate diagnosis is the basis of the right treatment.

03Scientific explanation

The suspicion stage. According to the NCI and ACS, the first step is a medical history, a physical examination and a complete blood count with differential. Anaemia, a low platelet count, a very high or very low white cell count and blasts in the blood are the main signals that raise the suspicion of leukemia. A blood smear shows the shape of the cells.

The confirmation stage. In acute leukemia, the diagnosis is usually confirmed by bone marrow aspiration and biopsy. Under the 2022 WHO classification, the general threshold for AML is at least 20% blasts in the marrow or blood, but with certain genetic changes (for example PML::RARA, RUNX1::RUNX1T1 or CBFB::MYH11) AML can be diagnosed with fewer blasts. In ALL, flow cytometry confirms that the blasts are lymphoid.

The characterisation stage. Flow cytometry (immunophenotyping) shows the cell lineage and how mature it is; cytogenetics (karyotype, FISH) shows chromosome changes; and molecular tests (PCR, NGS) show changes in genes such as FLT3, NPM1 and BCR::ABL1. According to ESMO guidelines, in AML these tests are needed for the diagnosis, the risk group and the choice of targeted drugs.

Additional tests. In some cases a lumbar puncture (spinal fluid test), heart tests, infection tests and imaging are done. These are less about the diagnosis itself and more about how far the disease has spread and how safe treatment will be.

04What happens in the body?

It starts with a suspicion

Most often the first signal is a blood count: low hemoglobin, low platelets and white cells that are either very high or very low. Sometimes the change is found by chance, on a routine test, with no symptoms at all — especially in chronic leukemias.

From blood to marrow

When a blood count raises a suspicion, the hematologist plans a bone marrow test. The sample is usually taken from the back of the hip bone under local anaesthetic. This lets doctors look directly at where the disease starts.

A small glowing test tube of blood on the left of a dark navy background, with a gentle path of light leading right to a glowing marrow cavity inside a translucent bone.
Figure 2.From a blood count to the bone marrow: the path from suspicion to confirmation.

One sample, several questions

The same marrow sample goes to different laboratories: microscopy (what percentage are blasts?), flow cytometry (which cell lineage?), cytogenetics (what has changed in the chromosomes?) and molecular tests (which genes?). Each answers its own question.

Four translucent lenses looking from four sides at one glowing drop of bone marrow in the centre of a dark navy background; a beam of a different colour comes from each lens and they meet in the middle.
Figure 3.One sample, four laboratory views, one answer.

The final diagnosis

When all the results are in, the hematologist puts them together: the type of leukemia (AML, ALL, CML, CLL and others), the subtype and the risk group. These decide the intensity of treatment, whether a transplant may be needed and which targeted drugs may help.

Why does it take time?

Microscopy and flow cytometry are often ready within a day or two, while chromosome and gene tests can take from a few days to two or three weeks. In an urgent situation, treatment starts on the first results and is refined later if needed.

05The road to a diagnosis: four stages

Each step answers the previous one’s question more precisely.

Suspicion — Symptoms, examination and a blood count.1SuspicionSymptoms, examination and a blood count.
Confirmation — Blood smear and bone marrow test.2ConfirmationBlood smear and bone marrow test.
Characterisation — Flow cytometry, chromosomes and genes.3CharacterisationFlow cytometry, chromosomes and genes.
Plan — Type and risk group shape treatment.4PlanType and risk group shape treatment.
An exact nameThe type and subtype of leukemia.
A risk groupThe expected course of the disease.
The right treatmentThe plan rests on the diagnosis.

06Which test answers which question

TestQuestionUsually ready
Complete blood countAre the numbers of blood cells normal?A few hours
Blood smearAre there blasts or unusual cells?1 day
Bone marrow microscopyWhat percentage of marrow cells are blasts?1–3 days
Flow cytometryWhich lineage is the cell (myeloid, B, T)?1–2 days
Cytogenetics (karyotype, FISH)Are there chromosome changes?FISH: a few days; karyotype: 1–3 weeks
Molecular tests (PCR, NGS)Which genes have changed?A few days to 2–3 weeks

* Timings depend on the hospital and laboratory. Tests that are needed urgently (for example PML::RARA in APL or FLT3 in AML) are often fast-tracked.

07Key terms

Complete blood count
A test that counts red cells, white cells and platelets in the blood.
Blast
An immature blood cell; blasts build up in acute leukemia.
Bone marrow aspiration
Removing the liquid part of the marrow with a needle.
Bone marrow biopsy
Removing a small core of marrow tissue.
Flow cytometry
A laboratory method that reads markers on the surface of cells.
Cytogenetics
Testing the number and structure of chromosomes.
Molecular test
A test that looks for specific gene changes.
Classification
The system for dividing leukemias into types and subtypes (WHO, ICC).
Risk group
A group based on the expected course of the disease; it guides treatment choices.

08Key points

  • A diagnosis comes from several tests together, not one.
  • A blood count raises the suspicion; the marrow usually confirms it.
  • Flow cytometry shows the cell lineage.
  • Chromosome and gene tests define the subtype and risk group.
  • Some results take two to three weeks — that is normal.
  • In urgent cases, treatment can start before every result is back.
  • Keep copies of all your reports.

09Frequently asked questions

Can a blood test tell for sure that it is leukemia?

A blood count can raise a strong suspicion, especially if blasts are seen in the blood. But to identify the type, subtype and risk group, a bone marrow test and laboratory tests are usually needed. In CLL, the diagnosis is often made from blood tests.

Why have I not been given an exact diagnosis yet?

Because some tests, especially genetic ones, take time. Your doctor does not want to draw conclusions from incomplete information. You can ask which results are still awaited and roughly when they will be ready.

Can the illness get worse while we wait?

In acute leukemia, doctors take this into account: if needed, treatment starts on the first results and is adjusted later. If you develop a fever, bleeding or breathlessness while waiting, seek help straight away.

Is a bone marrow test always necessary?

In acute leukemias and CML, usually yes. In CLL, not always: the diagnosis can be made by flow cytometry of the blood, and a marrow test is done in certain situations (for example before treatment).

Can I have my diagnosis checked by another doctor?

Yes. A second opinion is normal practice with serious diagnoses. You will need copies of all reports and, if possible, the slides.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Can a blood test tell for sure that it is leukemia?

  2. Why have I not been given an exact diagnosis yet?

  3. Can the illness get worse while we wait?

  4. Is a bone marrow test always necessary?

  5. Can I have my diagnosis checked by another doctor?

My questions

12Sources

  1. National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ®) — Patient Version
  2. National Cancer Institute (NCI). Adult Acute Lymphoblastic Leukemia Treatment (PDQ®) — Patient Version
  3. American Cancer Society. Tests for Acute Myeloid Leukemia (AML)
  4. American Cancer Society. Tests for Acute Lymphocytic Leukemia
  5. American Cancer Society. Tests for CML
  6. American Cancer Society. Tests for CLL
  7. NHS. Acute myeloid leukaemia — Tests and next steps
  8. Cancer Research UK. Bone marrow test
  9. MedlinePlus (U.S. National Library of Medicine). Bone Marrow Tests
  10. MedlinePlus (U.S. National Library of Medicine). Complete Blood Count (CBC)
  11. Blood Cancer United (formerly The Leukemia & Lymphoma Society). Acute myeloid leukemia (AML) diagnosis
  12. Leukemia (journal), 2022. Khoury JD et al. The 5th edition of the WHO Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
  13. Annals of Oncology (ESMO), 2020. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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