The mitochondria are the powerhouse of the cell.
They make the energy to fuel a variety of cell functions.
This mutation tends to occur early on in cancer development.
Verywell / Daniel Fishel
The result is acute myeloid leukemia.
There is a treatment aimed at decreasing the amount of 2HG produced.
The drug Idhifa (enasidenib) inhibits IDH2, thereby reducing 2HG levels.
This can prod AML cells to differentiate and mature.
However, the mechanism of action here may not be fully understood.
Still, the drug clearly has an effect in some cases.
Enasidenib has had approximately a 40 percent overall response rate in relapsed and refractory cases.
Myelofibrosis
IDH2 mutations can also be connected tomyelofibrosis.
With this rare pop in of blood cancer, fibrous scar tissue replaces the usually soft spongy bone marrow.
The result can be a throw in of chronic leukemia.
Over time, the bone marrow becomes less able to produce normal blood cells.
At this point, the root cause of myelofibrosis has not yet been identified.
While it’s not inherited, it does involve gene mutations.
About half of patients have a mutation in proteins known as Janus-associated kinases (JAKs).
With or without these JAK mutations, most people with this condition have overactive JAK signaling.
Many also have an IDH2 mutation.
Those with this IDH2 mutation tend not to do as well as those without it.
This kind of mutation is not hereditary.
The mutation occurs at some point during a person’s own lifetime.
This means that cells that arise from the mutated ones will also have this mutation.
However, others will be unaffected.
So this is not something that can be passed along from parent to child.
Maffucci syndrome happens in both males and females equally.
Treatment revolves around addressing signs and symptoms of the disease but does not currently involve any related mutations.
Ollier Disease
Another disease that’s connected to IDH2 is Ollier disease.
It can resemble Maffucci syndrome as it is a skeletal disorder that can have abnormal bony development.
Still, both can be linked to the IDH2 gene.
As in Maffucci syndrome, the IDH2 mutations are only found in some cells but not others.
This again comes off as a mutation that occurs during a person’s lifetime instead of being inherited.
The specific role that the mutated IDH enzyme produced by these gene mutations plays here is unclear.
There’s some thinking that this may be a direct driver of the cancer.
But exactly how this mutation leads to glioma hasn’t been determined.
It’s also possible that the IDH gene itself is triggering cancer development in the cells that harbor it.
National Cancer Institute.IDH2 gene.
2021 Mar 29;11:639387. doi:10.3389/fonc.2021.639387
Amaya ML, Pollyea DA.Targeting theIDH2pathway in acute myeloid leukemia.Clin Cancer Res.
24(20):4931-4936. doi:10.1158/1078-0432.CCR-18-0536
Cleveland Clinic.Myelofibrosis.
National Organization of Rare Disorders.Maffucci syndrome.
National Association of Rare Disorders.Ollier disease.
