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Diagnosis and tests

How genetics changes the type of leukemia

Two leukemias with the same name can be very different genetically. This topic explains how genetic changes in leukemia cells define the subtype, the risk group and the choice of treatment.

Last updated: ~3 min read
A translucent cell nucleus on a dark navy background with a glowing DNA strand and gold points along it.
Figure 1.Genetic changes shape the character of a leukemia.

01Short answer

Leukemia cells carry changes in chromosomes and genes. These are not inherited; they arise during life in blood-forming cells. They matter for three questions. First, the subtype: for example, t(15;17) PML::RARA defines APL, and BCR::ABL1 defines CML or Philadelphia-positive ALL. Second, the risk group: in AML, inv(16), t(8;21) and some NPM1 mutations are usually favourable, while a complex karyotype and TP53 changes are adverse. Third, treatment: changes such as FLT3, IDH1/IDH2 and BCR::ABL1 allow targeted drugs to be chosen. The risk group can also influence the decision about a transplant.

02Simple explanation

A gene is an instruction. Every cell has instructions for when to divide and when to mature. In leukemia, several of these instructions are broken.

Somatic change. These faults are not present from birth; they arise later, only in blood cells. So they are not passed on to family.

Changes that give a name. Some changes are so important that the disease is named after them.

Changes that change the plan. Some can be “targeted” with a specific drug; others affect the transplant decision.

03Scientific explanation

Risk groups: according to the NCI and ESMO, genetic risk in AML is usually split into three groups: favourable (for example inv(16)/t(16;16), t(8;21), NPM1 mutation without FLT3-ITD), intermediate and adverse (complex karyotype, TP53 mutation and some other changes). The grouping is updated by ELN recommendations.

Targeted treatment: according to the NCI, FLT3 inhibitors are used in FLT3-mutated AML, IDH inhibitors with IDH1/IDH2 mutations, and tyrosine kinase inhibitors in CML and Ph+ ALL with BCR::ABL1. In APL, ATRA and arsenic trioxide act specifically on PML::RARA.

Inherited predisposition: rarely (for example in RUNX1, CEBPA or DDX41) there is an inherited predisposition. This matters especially when choosing a family donor for a transplant; your doctor may offer genetic counselling if needed.

04What happens in the body?

When do genetic results arrive?

FISH and some PCR tests take a few days; a karyotype and broad NGS panels take one to three weeks. Tests that need a fast answer (such as PML::RARA for APL, or FLT3) are usually done first.

A long and a short glowing chromosome joined by a bright gold and teal segment.
Figure 2.BCR::ABL1: two genes joined together.

What does the risk group affect?

The choice of consolidation: chemotherapy alone or an allogeneic transplant in remission. It also affects which marker is used to track residual disease during treatment.

Three lit paths of different widths crossing a dark plain toward a calm horizon.
Figure 3.A risk group shows different paths; it does not take away hope.

Can the result change over time?

At relapse, leukemia can gain new changes. So genetic tests are repeated if it returns, which may open the option of a new targeted drug.

05From sample to targeted plan

How genetic information becomes treatment.

Sample — Blood or bone marrow.1SampleBlood or bone marrow.
Analysis — Karyotype, FISH, NGS.2AnalysisKaryotype, FISH, NGS.
Risk group — Favourable, intermediate, adverse.3Risk groupFavourable, intermediate, adverse.
Plan — Targeted drug, transplant decision.4PlanTargeted drug, transplant decision.
SubtypeGenetic name.
RiskEstimating the outlook.
TargetA matching drug.

06Some genetic changes and what they mean

ChangeWhere?Why does it matter?
t(15;17) PML::RARAAPLSpecial treatment with ATRA and arsenic
inv(16) / t(8;21)AML (CBF)Usually favourable risk
NPM1AMLOften favourable without FLT3-ITD; MRD marker
FLT3-ITD/TKDAMLAn FLT3 inhibitor is added
BCR::ABL1CML, Ph+ ALLTyrosine kinase inhibitors
TP53, complex karyotypeAMLAdverse risk, different approach

* The table is simplified; your doctor will explain your result.

07Key terms

Somatic mutation
A change that arises during life and is not inherited.
Translocation
An exchange of pieces between two chromosomes.
Fusion gene
A new gene formed by joining two genes.
Risk group
An estimate of the expected course based on genetics.
Targeted therapy
A drug that acts on a specific molecular change.
ELN
European LeukemiaNet recommendations.

08Key points

  • Genetic changes are usually not inherited.
  • They define the subtype.
  • They shape the risk group.
  • They allow a targeted drug to be chosen.
  • They influence the transplant decision.
  • Tests are repeated at relapse.

09Frequently asked questions

Will my children carry this change?

Usually not: the changes are only in the leukemia cells. If a rare inherited form is suspected, your doctor will offer genetic counselling.

My risk group is adverse. What does that mean?

It means standard treatment alone may not be enough and your doctor may suggest a stronger or different path. Individual courses can still differ.

How long does a genetic test take?

Depending on the test, from a few days to three weeks.

Does everyone get a targeted drug?

No, only when a matching change is found and your doctor considers it suitable.

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. Will my children carry this change?

  2. My risk group is adverse. What does that mean?

  3. How long does a genetic test take?

  4. Does everyone get a targeted drug?

My questions

12Sources

  1. American Cancer Society. Acute Myeloid Leukemia (AML) Subtypes and Prognostic Factors
  2. National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ) – Patient Version
  3. National Cancer Institute (NCI). Chronic Myeloid Leukemia Treatment (PDQ) – Patient Version
  4. Leukemia & Lymphoma Society. Genetic testing and AML
  5. MedlinePlus Genetics. Cytogenetically normal acute myeloid leukemia
  6. ESMO. ESMO Clinical Practice Guidelines: Haematological Malignancies
  7. Cancer Research UK. Symptoms of acute myeloid leukaemia (AML)
  8. NHS. Acute leukaemia: Diagnosis
  9. MedlinePlus. Infectious Mononucleosis
  10. MedlinePlus. Iron-deficiency anemia
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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