JAK2 Mutations Rare, With Unclear Implications in MDS

A new report found only about 2.8% of people with myelodysplastic syndromes (MDS) have JAK2 mutations.

A new report is shining a light on an uncommon—but potentially meaningful—characteristic of some patients with myelodysplastic syndromes (MDS): Janus kinase 2 (JAK2) mutations.

The review article and case report, published in Hematology Reports, confirmed that JAK2 mutations are rare in MDS, but also found that the specific mutations identified in people with MDS are diverse. The authors said the variants they found may be associated with a myelodysplastic phenotype.

One consequence of the rarity of JAK2 mutations is that it is not yet clear what impact—if any—they have on a patient’s prognosis, explained the study authors. The significant major studies of the mutations thus far have found conflicting results, they noted.

Of the studies attempting to figure out how JAK2 mutations affect outcomes in MDS specifically, 1 study found patients with themutations led to better survival and a lower rate of progression to acute myeloid leukemia (AML). However, a larger study of patients undergoing allogeneic hematopoietic stem cell transplantation suggested that JAK2 mutations were associated with shorter survival.

To better understand the role of JAK2 mutations in MDS, the investigators conducted an institutional review to identify cases of MDS between January 2020 and April 2022. They excluded cases of myelodysplastic/myeloproliferative overlap syndrome, including those with ring sideroblasts and thrombocytosis.

Cases where molecular data were available were analyzed via next-generation sequencing in order to identify JAK2 mutations. The investigators also conducted a literature review of studies involving JAK2 mutations in MDS.

The investigators found 107 cases of MDS that were reviewable. Of those, JAK2 mutations were present in just 3 cases, of which just 1 involved a JAK2 V617Fmutation. That mutation is typically associated with myeloproliferative neoplasms (MPNs).

“In addition, we found JAK2 R564L andJAK2 I670V point mutation variants to be associated with a myelodysplastic phenotype,” they said.

The authors also presented 3 cases that underscored the challenges of delivering a correct diagnosis to patients with MDS and JAK2 mutations. They summarized their findings into 3 key takeaways.

“First, JAK2 V617F mutations are extremely rare in MDS and, in its presence, an MPN must be excluded,” they wrote. “Second, JAK2 mutations are diverse and JAK2 variant mutations may lead to a myelodysplastic syndrome phenotype.” Lastly, they said that although variants such as JAK2 R564L and JAK2 I670V might be associated with a myelodysplastic phenotype, it is not yet clear what role they might play in patient outcomes.

“While the JAK2 I670V mutation has been reported at low frequency in the European population, its exact impact on the pathogenesis of MDS may be arguable and further studies are recommended to investigate the relationship between JAK2 mutation variants and their clinico-morphologic phenotypes,” they wrote.

The authors said it was not possible to draw definitive conclusions about the prognostic relevance of JAK2 mutations, given that their study only involved 3 cases, of which just 1 transformed to AML. They said further study is needed to better understand not just the prevalence of the mutations, but their implications for patients.


Delio M, Bryke C, Mendez L, Joseph L, Jassim S. JAK2 mutations are rare and diverse in myelodysplastic syndromes: case series and review of the literature. Hematol Rep. 2023;15(1):73-87. doi:10.3390/hematolrep15010008

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