FLT3 Mutations in Acute Myeloid Leukemia

Section Editor: Kamran Mirza MD PhD
September 5, 2026

If your bone marrow or blood test results mention an FLT3 mutation, this refers to a change in a gene that controls how blood-forming cells grow and divide. FLT3 mutations are among the most common molecular findings in acute myeloid leukemia, found in roughly 30 percent of adults with the disease. There are two types, FLT3-ITD and FLT3-TKD. They behave differently, carry different implications for outlook, and are both targets for a group of drugs called FLT3 inhibitors.

This article explains what each type of FLT3 mutation is, how the result is reported, and how it shapes treatment. It also explains a change made to the risk classification system in 2022 that affects how the FLT3 result is now used. Older reports and older websites do not reflect that change.

What is FLT3, and what do these mutations do?

The FLT3 gene provides instructions for making a protein, also called FLT3, that sits on the surface of blood-forming cells in the bone marrow. FLT3 works like a receiver. When the right signal arrives from outside the cell, it activates briefly and tells the cell to grow and divide. When the signal passes, it switches off again. In acute myeloid leukemia, two different kinds of mutations break that off switch.

FLT3-ITD is an internal tandem duplication. A short stretch of the gene is copied and inserted twice, back to back, like a word typed twice in a row. The extra material sits inside the part of the protein that normally holds the receiver in the off position. With it in place, the protein stays switched on, continuously telling leukemia cells to divide. FLT3-ITD is found in about 25 percent of adults with acute myeloid leukemia.
FLT3-TKD is a tyrosine kinase domain mutation—a single letter in the code changes within the part of the protein that sends the growth signal. The most common is called D835. This also leaves the protein switched on by altering the signaling machinery directly, rather than disabling the off switch. FLT3-TKD is found in about 5 to 10 percent of cases.

Why is the test done?

FLT3 testing is part of the standard molecular workup for everyone newly diagnosed with acute myeloid leukemia. The result does two things. It contributes to the risk group, which estimates how likely the leukemia is to return after treatment. It also identifies people who can be treated with a FLT3 inhibitor, which is now given from the start of treatment rather than only after the leukemia returns.

Testing is repeated if the leukemia comes back, because FLT3 status can change. A leukemia that had no FLT3 mutation at diagnosis can acquire one at relapse, and a FLT3 mutation present at diagnosis can disappear. Repeat testing means treatment decisions are based on the leukemia’s current biology rather than its original profile.

How is the test performed?

FLT3 mutations are detected in leukemia cells taken from a bone marrow biopsy, or from a blood sample when large numbers of blasts are circulating. Two laboratory approaches are used, often together.

Fragment analysis combined with sequencing is a targeted test that examines only the regions of the FLT3 gene where these mutations occur. It is fast and reliable and remains the reference method for FLT3-ITD. Next-generation sequencing reads many genes at once and is increasingly the main diagnostic platform because the full combination of mutations present predicts behavior better than FLT3 alone. Standard sequencing can miss small FLT3-ITD insertions or measure them inaccurately, which is why dedicated fragment analysis is still performed alongside it when FLT3-ITD is specifically in question.

How are results reported?

A FLT3 result is reported separately for each type of mutation, as FLT3-ITD detected or not detected, and FLT3-TKD detected or not detected. The specific change is usually described. For an ITD, this is the size in base pairs of the inserted sequence, and for a TKD mutation it is a name such as FLT3 D835Y.

For FLT3-ITD, many laboratories also report an allelic ratio, and some report a variant allele frequency instead. Both describe how much of the mutation is present. What that number is used for has changed, as explained in the next section.

The allelic ratio, and why it no longer sets the risk group

The allelic ratio for a FLT3-ITD mutation compares the amount of mutated FLT3 in the sample with the amount of normal FLT3. A ratio of 0.5 means there is half as much mutated as normal. A ratio above 0.5 means there is more mutated than normal, which happens when leukemia cells lose the normal copy or duplicate the mutated one.

For many years, this number divided FLT3-ITD results into high- and low-burden groups at a cutoff of 0.5, and that division changed the risk group. The 2022 revision of the European LeukemiaNet risk classification removed it. The reason was practical, not biological. Different laboratories measured the ratio differently, and results varied by method and by the proportion of leukemia cells in the sample. Centers could not apply the cutoff consistently.

Two things follow from this change.

Any FLT3-ITD now falls into the intermediate-risk group, provided no adverse-risk change is also present. This applies whether the ratio is high or low, and whether or not an NPM1 mutation is present alongside it.
An NPM1 mutation with any FLT3-ITD is intermediate, not favorable. Under the previous system, NPM1 with a low-burden FLT3-ITD was classified as favorable. A report or website from before 2022 may therefore describe the same result more optimistically than the current system does.

The number has not disappeared from practice. Many laboratories still report it, some treatment protocols and clinical trials still use it, and some teams still weigh it when deciding about a stem cell transplant. If it appears on your report, it is reasonable to ask what your team does with it, rather than assuming it sets your risk group.

What does the result mean?

What a FLT3 result means for you depends on which type of mutation was found and on what else was found alongside it. Never interpret FLT3 on its own.

FLT3-ITD detected. The leukemia cells are being driven by a permanently switched-on FLT3 receptor. FLT3-ITD is associated with a higher white blood cell count at diagnosis and a higher rate of early relapse after chemotherapy alone. It places the leukemia in the intermediate risk group unless an adverse-risk change is also present, in which case the adverse finding takes precedence. FLT3 inhibitors have substantially changed the outlook for this group.
FLT3-TKD detected. A point mutation in the signaling part of the protein. On its own, it does not move the leukemia into a higher risk group in the current classification. It still matters, because some FLT3 inhibitors are active against TKD mutations and some are not.
Both detected. Uncommon. The ITD result drives the risk group, and inhibitor choice takes both into account.
Neither detected. The other findings, including NPM1, CEBPA, IDH1, IDH2, TP53, and the chromosome result, guide risk classification and treatment. A negative result at diagnosis does not rule out FLT3 involvement if the leukemia returns, which is why testing is repeated then.

FLT3 inhibitors

FLT3 inhibitors bind to the FLT3 protein and block its ability to send growth signals, removing a driver that the leukemia cells depend on. Three are approved for acute myeloid leukemia, and which one is used depends on the mutation type and on whether the leukemia is newly diagnosed or has returned.

Midostaurin. Added to standard induction chemotherapy for newly diagnosed FLT3-mutated leukemia in people fit for intensive treatment. In the RATIFY trial, it improved survival compared with chemotherapy alone, with roughly 51 percent alive at four years versus roughly 44 percent. It is active against both ITD and TKD mutations.
Quizartinib. Approved for newly diagnosed FLT3-ITD-positive leukemia, given with induction and consolidation chemotherapy and continued afterward as maintenance. In the QuANTUM-First trial, roughly 33 percent of people were alive at three years, compared with roughly 26 percent with chemotherapy alone. It is specific to FLT3-ITD and has no useful activity against TKD mutations.
Gilteritinib. A more selective inhibitor approved for leukemia that has returned or has not responded. In the ADMIRAL trial,l median survival was roughly 9.3 months, compared with roughly 5.6 months with standard salvage chemotherapy. It is active against both ITD and TKD mutations, including some that resist other FLT3 inhibitors.

FLT3 inhibitors are also used as maintenance after a stem cell transplant. The benefit appears greatest in people who still have detectable leukemia at very low levels when maintenance begins.

FLT3 and stem cell transplantation

A FLT3-ITD result is one of the findings that prompts discussion of an allogeneic stem cell transplant in first remission. In this procedure, blood-forming cells from a donor replace your bone marrow after high-dose treatment, and the donor immune system helps control any remaining leukemia.

The decision is not made on FLT3 status alone. Age, general health, whether a suitable donor is available, and how completely the leukemia clears after the first round of chemotherapy all weigh in. Residual disease testing after induction has become one of the most influential factors. In some centers, a person with FLT3-ITD who clears the marrow completely receives less intensive treatment than the mutation alone would suggest.

Measurable residual disease

After treatment, sensitive tests look for very small amounts of leukemia that cannot be seen under a microscope. This is called measurable residual disease, abbreviated MRD, and older reports may call it minimal residual disease. Finding residual leukemia after chemotherapy is associated with a higher risk of relapse and can change the decision about transplant or maintenance treatment.

FLT3-ITD is a more difficult MRD marker than some others. The mutation can change between diagnosis and relapse, so a leukemia that returns may no longer carry it, and detecting small insertions at very low levels is technically demanding. For this reason, MRD is often followed using PCR for another marker, such as an NPM1 mutation, or by flow cytometry. Your team will explain which method applies in your case.

What happens next?

For most people newly diagnosed with FLT3-mutated acute myeloid leukemia who are fit for intensive treatment, the next step is induction chemotherapy combined with a FLT3 inhibitor. This is usually midostaurin or quizartinib, depending on the mutation type. Treatment begins quickly, because acute myeloid leukemia can progress over days to weeks.

After induction, a repeat bone marrow test checks whether the leukemia has gone into remission. If it has, consolidation treatment follows, and this is usually when the discussion about a stem cell transplant takes place. For people who are not fit for intensive chemotherapy, lower-intensity combinations are used, sometimes with a FLT3 inhibitor added.

If the leukemia returns or does not respond, doctors repeat FLT3 testing, and gilteritinib is the most commonly used targeted option. At this point, clinical trials are also discussed, including combinations of FLT3 inhibitors with other targeted drugs.

Questions to ask your doctor

Do I have a FLT3-ITD mutation, a FLT3-TKD mutation, or both?
Which risk group does my FLT3 result place me in, once all my other results are taken into account?
My report gives an allelic ratio. Does your team use that number for anything, given that it was removed from the risk classification in 2022?
Do I also have an NPM1 mutation, and how do the two results together affect my outlook?
Which FLT3 inhibitor is being recommended, and will it be given with chemotherapy, on its own, or as maintenance?
Is a stem cell transplant being considered, and when would that decision be made?
Will residual disease be measured after treatment, and which marker will be used?
If FLT3-ITD is not a good marker for monitoring in my case, what will be used instead?
If my leukemia comes back, will FLT3 testing be repeated?
Are there clinical trials involving FLT3-targeted treatments that I should know about?