Mutations in Triple Negative Essential Thrombocytopenia Detected

Atypical mutations were found in the thrombopoietin receptor (MPL) in patients with triple negative essential thrombocytopenia (ET), according to an article published online ahead of print in Blood.¹

Investigators used whole exome sequencing and next generation sequencing to detect mutations in 17 ET samples that were negative for JAK2V617F, MPLW515K/L, and CALR mutations. JAK2V617F at low-allele frequency, two MPLS204P signaling mutations, and one of each of the following signaling mutations: SH2B3, MPLS505N, MPLW515R, were found.

Clonal and polyclonal hematopoiesis were detected in four and seven samples, respectively. This suggests that some cases of triple-negative ET are not myeloproliferative neoplasms.

After next genome sequencing on an additional 26 triple-negative samples, only one MPLY591N mutation was detected and was found to be a weak gain-of-function. MPLS204P was also found to be weak gain-of-function after functional studies.

These mutations increase MPL signaling and may induce TPO hypersensitivity or function without expressing cells, but with little effect.

Investigators suggest additional studies to determine the frequency of MPLS204 and MPLY591 in a larger cohort of triple-negative ET patients.

Reference

1. Cabagnols X, Favale F, Pasquier F, et al. Presence of atypical thrombopoietin receptor (MPL) mutations in triple negative essential thrombocytopenia patients [published online ahead of print October 8, 2015]. Blood. doi: 10.1182/blood-2015-07-661983.