The disease as families live it
Start to finish: the first symptoms a parent notices, how the diagnosis is made, what treatment involves for a baby, and what published accounts and case reports tell us about the course.
She already had it at birth
The fusion is already present on the day of birth — found in the child's own archived newborn blood spot — and the leukaemia usually appears within the first two years. For every other childhood fusion that starts before birth, the gap is years. That short latency is the fact everything else on this page has to fit around.
Two properties are left off the chart on purpose. Every one of these entries carries published counter-evidence, and every one records its own open questions — both are requirements of the schema rather than findings, so a bar for either could not move, and a statistic that cannot move cannot tell you anything. All of them also carry a bite_back note on how the idea could hurt someone.
A child who made a KMT2A fusion during chemotherapy, lost it again, and never got leukaemia in 12.8 years
A child being treated for high-risk neuroblastoma developed a cell clone carrying a KMT2A fusion - the kind that normally means leukaemia. It was there, at low level, and then it was gone, and after nearly thirteen years of follow-up the child never developed leukaemia.
A five-year-old with KMT2A::USP2 ALL whose MRD would not clear until blinatumomab, then transplant, then more blinatumomab
A five-year-old boy's leukaemia kept showing traces after standard treatment. One course of an antibody drug cleared those traces, he had a transplant from a half-matched donor, and then more of the same antibody plus donor immune cells to stop it coming back. He stayed in remission with only mild side effects.
A KMT2A fusion acquired at seventy-three: KMT2A::ELL AML arising out of polycythaemia vera, and a menin inhibitor used to hold the line
A man with a chronic blood disorder diagnosed at seventy-one became progressively anaemic and transfusion-dependent, and over about five weeks his marrow scarred and then turned into acute leukaemia - carrying the same kind of broken KMT2A gene that infants are born with. Standard low-intensity treatment stopped working after about a year, and a menin inhibitor, the same class used in children, held his disease stable without complete remission for the four months reported.
A nine-month-old with AML whose fusion was found only after every standard test failed
A nine-month-old boy had acute myeloid leukaemia that tests said was KMT2A-related, but no test could say what KMT2A was joined to. Sequencing all his cells' RNA finally showed it was joined to USP2 - the first time this had been seen in AML.
A six-month-old with a week of coughing: KMT2A::AFF1 pro-B ALL presenting with extreme hyperleukocytosis
A six-month-old boy was brought in after a week of coughing and wheezing that had been treated as a chest problem; the blood count that was finally sent showed a white cell count hundreds of times too high and a haemoglobin of 49 g/L. Two sessions of a machine that filters white cells out of the blood, then chemotherapy, brought him into remission, and at thirteen months of age he was growing normally.
Born with it: congenital KMT2A::MLLT1-type AML, a subdural haemorrhage that began before birth, and death on day four
A baby girl was delivered at 36 weeks because her heart rate was dropping, and was born already ill: a purple rash all over, a hugely enlarged liver and spleen, unequal pupils and a weak left side. Her white cell count was 188,000, her blood would not clot, and scans showed a large bleed inside her skull that had probably started before she was born; after her family were told what the options were, they chose comfort care and she died on the fourth day of her life.
Fever and headache thirty-two months after transplant: KMT2A::AFDN AML relapsing into the CNS, and a menin inhibitor that cleared the spinal fluid
A man in his early thirties was admitted with a fever of 39.8 C, bleeding gums and a chest infection, and was found to have acute myeloid leukaemia. Chemotherapy and a transplant kept him well for nearly three years, but he came back with fever and a headache and the leukaemia had moved into his spinal fluid, where nearly two thirds of the cells were blasts; a menin inhibitor combined with two other drugs and an infusion of donor immune cells cleared both his marrow and his spinal fluid, and he was still in remission six months later.
Infant acute lymphoblastic leukaemia (ALL diagnosed under 1 year of age)
Infant ALL is leukaemia of the blood-forming system diagnosed in a baby under one year old, and in about three quarters of these babies the cause is a broken KMT2A gene. It behaves like a different disease from the leukaemia of older children: the babies arrive sicker, most of them relapse while still on treatment, and only about half are alive six years later.
KMT2A-rearranged acute lymphoblastic leukaemia
Acute lymphoblastic leukaemia in which the KMT2A gene on chromosome 11 has broken and joined another gene. It is the defining lesion of leukaemia in babies under one year old, and it responds far worse to standard treatment than other childhood ALL.
KMT2A-rearranged acute myeloid leukaemia in children and infants
The same broken KMT2A gene that causes leukaemia of the B-cell lineage in babies can instead produce myeloid leukaemia, which fills the marrow with a different kind of immature cell. Which partner gene KMT2A joins matters enormously here: across children with 11q23-rearranged myeloid leukaemia, five-year event-free survival ranges from about 11% to about 92% depending on the partner.
KMT2A-rearranged soft tissue sarcoma - the same gene as infant B-ALL, in a young adult's leg, as a solid tumour
A rare soft-tissue cancer of young adults is driven by a rearrangement of KMT2A - the same gene whose rearrangement causes infant leukaemia - but it grows as a solid lump in muscle or limb rather than in blood, and it often spreads. There are two forms: a dense, scar-like one with a YAP1 partner, and a more uniformly cellular one with a vimentin partner.
KMT2A::MAML2 type B2/B3 thymoma - the same fusion, a different organ, a different disease
The same KMT2A fusion that causes leukaemia in children also causes a tumour of the thymus in middle-aged adults. That one fusion produces two completely different diseases depending on which cell it lands in is the clearest natural experiment this graph has about what a fusion needs in order to cause leukaemia.
Mixed phenotype acute leukaemia (MPAL) and acute leukaemia of ambiguous lineage
In a few children the leukaemia cells do not commit to being either the lymphoid kind or the myeloid kind, and carry markers of both - sometimes as two separate populations in the same marrow. It matters practically, because which of the two standard treatment programmes the child is put on changes survival more than almost any other decision.
NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door
About one in five babies with leukaemia who do NOT have the usual KMT2A rearrangement instead have a NUTM1 rearrangement. It is the same disease in the same age group, but almost all of these children are cured by ordinary chemotherapy, while the KMT2A group is the hardest leukaemia in paediatrics to cure.
p279 and p318: one infant, two diseases, and an oncoprotein target map that does not carry over
One baby's leukaemia started as a B-cell type, was treated, and came back as a myeloid type. Profiling the cancer protein in both shows the list of genes it controls changed as much as if it were a different child.
Pancreatic neuroendocrine tumours in MEN1: the manifestation that kills, and the one the animal data points at
About half of people with a broken menin gene develop tumours in the hormone-making cells of the pancreas, and these are the MEN1 tumours most likely to be fatal. In children with MEN1 they appear as insulin-producing tumours in about one in eight.
Pituitary adenoma in MEN1: the third manifestation, and the one that matters most for a growing child
About a third of people with a faulty menin gene grow a tumour in the pituitary, the gland at the base of the brain that controls growth and puberty. It was the first sign of disease in a third of patients whose MEN1 began before they turned 21.
Primary hyperparathyroidism in MEN1: the first and commonest consequence of losing menin
When a person inherits one broken copy of the menin gene, the parathyroid glands in the neck are almost always the first to go wrong, over-producing the hormone that controls blood calcium. It reaches roughly 90% of carriers by late life and it is the earliest thing that shows up.
Six relapses and a change of lineage: KMT2A::AFDN T-lymphoblastic lymphoma that came back as monoblastic leukaemia, and a seventh remission that held
A 27-year-old man was diagnosed with a T-cell lymphoma growing as a mass in his chest; it came back five times, in his brain and spinal fluid and in his marrow. At the sixth relapse the disease had changed type entirely, from a T-cell lymphoma into a myeloid leukaemia - but the same genetic fault was in both, proving it was the same disease wearing a different face, and after one course of an antibody drug and a cord blood transplant he had been in remission for more than three years.
Skin first, blood later: a three-day-old referred for purple spots, with KMT2A::MLLT3 neonatal ALL
A newborn who seemed completely well was referred at three days old because of purple, non-fading marks on his face and shoulder; his blood count was normal and no leukaemia cells could be found in it. A skin biopsy on day seven showed the leukaemia, the marks faded and then came back everywhere, and by day 24 his white cell count had climbed to 125,700 - he was treated with chemotherapy and a stem cell transplant and was well at two years old.
The first published complete remission of NUP98-rearranged AML on a menin inhibitor (icovamenib/BMF-219, n=1)
A 39-year-old man whose leukaemia came back after a bone-marrow transplant was given a menin-blocking drug and went into complete remission within three months, with no detectable disease left. Six months later the leukaemia returned, carrying a handful of new mutations that had nothing to do with the drug's target.
The leukaemia that changed lineage in eleven days and changed back when the drug stopped: KMT2A::AFF4 infant ALL on blinatumomab
A girl diagnosed with B-cell leukaemia at five months old relapsed after a transplant and was given blinatumomab, an antibody that directs the immune system against B cells. Within eleven days her leukaemia had stopped being a B-cell leukaemia and become a myeloid one - and when the drug was stopped it turned back into a B-cell leukaemia within days; she later developed solid deposits of leukaemia outside the marrow and died.
Three pairs of twins who both got leukaemia: the patients who proved the fusion happens before birth
Three pairs of infant twins each developed leukaemia, and in each pair both babies' leukaemia cells carried exactly the same, individually unique break in the same gene - a break that was not in their normal cells. Since the same accident cannot happen twice by chance in two different children, the cells must have been shared between them before birth, which is how the world learned that infant leukaemia starts in the womb.
Two clones, two antibodies: a four-month-old with refractory KMT2A::AFF1 mixed-phenotype leukaemia treated with blinatumomab and gemtuzumab together
A four-month-old girl arrived exhausted, pale, bruising and struggling to breathe, with a white cell count of 762,000 and blood that would not clot properly; her leukaemia turned out to be two different diseases in one child, a B-cell one and a myeloid one. Chemotherapy failed three times, so her doctors gave two antibody drugs together, each aimed at one of the two clones, which worked well enough for a transplant; she relapsed eleven months later, was rescued again with CAR-T cells, and was alive and in remission at three years old.