BRCA1 and BRCA2 gene mutations may play a role in the development of familial myeloproliferative neoplasms (MPNs), according to research published in Blood Advances.

MPNs have previously been linked with JAK2, CALR, and MPL. There is, furthermore, evidence that inheritance may play a role in MPNs, with familial disease occurring in up to 8% of all cases. The JAK2 46/1 haplotype, for example, is linked with up to a 400% increased risk of MPNs.

It is, however, unclear to what degree other germline variants may play a role in MPN development. For this study, researchers aimed to identify, using whole exome-sequencing, any consistently detectable germline variants in a group of 5 families with a history of MPNs.

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All included families had either parent-child pairs or sibling pairs both diagnosed with MPNs; all included families were carries of the JAK2 V617F variant. In 4 (80%) of the familial groups, the researchers noted genes linked with tumor predisposition, including BRCA1 and BRCA2.

In 1 of the families, a female sibling with a loss-of-function mutation in BRCA1 developed both MPN and uterine cancer within 8 years of each other.

As previous research suggests that use of ruxolitinib may decrease BRCA levels in JAK2 V617F–mutant MPN, patients with BRCA1/2 mutations and MPN may respond to poly (ADP-ribose) polymerase (PARP) inhibition.

“In summary, the data suggest that MPNs are more frequently triggered by germline mutations than previously assumed, and conversely, the spectrum of known tumor predisposition syndromes seems to be broader than anticipated,” the authors wrote.


Elbracht M, Meyer R, Kricheldorf K, et al. Germline variants in DNA repair genes, including BRCA1/2, may cause familial myeloproliferative neoplasms. Blood Adv. 2021;5(17):3373-3376. doi:10.1182/bloodadvances.2021004811